Pesticidal compositions

ABSTRACT

The present invention concerns novel heteroaryl-N-aryl thiosemicarbazones and their use in pest control, as insecticides and acaπcides This invention also includes preparation of the pesticide compositions containing the compounds, and methods of controlling insects using the compounds

FIELD OF THE INVENTION

This application claims the benefit of U.S. Provisional Application Ser.No. 61/232,152 filed on 7 Aug. 2009, the entire contents of which arehereby incorporated by reference. The invention disclosed in thisdocument is related to the field of pesticides and their use incontrolling pests.

BACKGROUND OF THE INVENTION

Pests cause millions of human deaths around the world each year.Furthermore, there are more than ten thousand species of pests thatcause losses in agriculture. These agricultural losses amount tobillions of U.S. dollars each year. Termites cause damage to variousstructures such as homes. These termite damage losses amount to billionsof U.S. dollars each year. As a final note, many stored food pests eatand adulterate stored food. These stored food losses amount to billionsof U.S. dollars each year, but more importantly, deprive people ofneeded food.

There is an acute need for new pesticides. Insects are developingresistance to pesticides in current use. Hundreds of insect species areresistant to one or more pesticides. The development of resistance tosome of the older pesticides, such as DDT, the carbamates, and theorganophosphates, is well known. But resistance has even developed tosome of the newer pesticides. Therefore, a need exists for newpesticides and particularly for pesticides that have new modes ofaction.

Substituents (Non-Exhaustive List)

The examples given for the substituents are (except for halo)non-exhaustive and must not be construed as limiting the inventiondisclosed in this document.

“alkenyl” means an acyclic, unsaturated (at least one carbon-carbondouble bond), branched or unbranched, substituent consisting of carbonand hydrogen, for example, vinyl, allyl, butenyl, pentenyl, hexenyl,heptenyl, octenyl, nonenyl, and decenyl.

“alkenyloxy” means an alkenyl further consisting of a carbon-oxygensingle bond, for example, allyloxy, butenyloxy, pentenyloxy, hexenyloxy,heptenyloxy, octenyloxy, nonenyloxy, and decenyloxy.

“alkoxy” means an alkyl further consisting of a carbon-oxygen singlebond, for example, methoxy, ethoxy, propoxy, isopropoxy, 1-butoxy,2-butoxy, isobutoxy, tert-butoxy, pentoxy, 2-methylbutoxy,1,1-dimethylpropoxy, hexoxy, heptoxy, octoxy, nonoxy, and decoxy.

“alkyl” means an acyclic, saturated, branched or unbranched, substituentconsisting of carbon and hydrogen, for example, methyl, ethyl, propyl,isopropyl, 1-butyl, 2-butyl, isobutyl, tert-butyl, pentyl,2-methylbutyl, 1,1-dimethylpropyl, hexyl, heptyl, octyl, nonyl, anddecyl.

“alkynyl” means an acyclic, unsaturated (at least one carbon-carbontriple bond, and any double bonds), branched or unbranched, substituentconsisting of carbon and hydrogen, for example, ethynyl, propargyl,butynyl, pentynyl, hexynyl, heptynyl, octynyl, nonynyl, and decynyl.

“alkynyloxy” means an alkynyl further consisting of a carbon-oxygensingle bond, for example, pentynyloxy, hexynyloxy, heptynyloxy,octynyloxy, nonynyloxy, and decynyloxy.

“aryl” means a cyclic, aromatic substituent consisting of hydrogen andcarbon, for example, phenyl, naphthyl, and biphenyl.

“cycloalkenyl” means a monocyclic or polycyclic, unsaturated (at leastone carbon-carbon double bond) substituent consisting of carbon andhydrogen, for example, cyclobutenyl, cyclopentenyl, cyclohexenyl,cycloheptenyl, cyclooctenyl, cyclodecenyl, norbornenyl,bicyclo[2.2.2]octenyl, tetrahydronaphthyl, hexahydronaphthyl, andoctahydronaphthyl.

“cycloalkenyloxy” means a cycloalkenyl further consisting of acarbon-oxygen single bond, for example, cyclobutenyloxy,cyclopentenyloxy, cyclohexenyloxy, cycloheptenyloxy, cyclooctenyloxy,cyclodecenyloxy, norbornenyloxy, and bicyclo[2.2.2]octenyloxy.

“cycloalkyl” means a monocyclic or polycyclic, saturated substituentconsisting of carbon and hydrogen, for example, cyclopropyl, cyclobutyl,cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, cyclodecyl, norbornyl,bicyclo[2.2.2]octyl, and decahydronaphthyl.

“cycloalkoxy” means a cycloalkyl further consisting of a carbon-oxygensingle bond, for example, cyclopropyloxy, cyclobutyloxy, cyclopentyloxy,cyclohexyloxy, cycloheptyloxy, cyclooctyloxy, cyclodecyloxy,norbornyloxy, and bicyclo[2.2.2]octyloxy.

“halo” means fluoro, chloro, bromo, and iodo.

“haloalkyl” means an alkyl further consisting of, from one to themaximum possible number of, identical or different, halos, for example,fluoromethyl, difluoromethyl, trifluoromethyl, 1-fluoromethyl,2-fluoroethyl, 2,2,2-trifluoroethyl, chloromethyl, trichloromethyl, and1,1,2,2-tetrafluoroethyl.

“heterocyclyl” means a cyclic substituent that may be fully saturated,partially unsaturated, or fully unsaturated, where the cyclic structurecontains at least one carbon and at least one heteroatom, where saidheteroatom is nitrogen, sulfur, or oxygen, for example, benzofuranyl,benzoisothiazolyl, benzoisoxazolyl, benzoxazolyl, benzothienyl,benzothiazolyl cinnolinyl, furanyl, indazolyl, indolyl, imidazolyl,isoindolyl, isoquinolinyl, isothiazolyl, isoxazolyl, 1,3,4-oxadiazolyl,oxazolinyl, oxazolyl, phthalazinyl, pyrazinyl, pyrazolinyl, pyrazolyl,pyridazinyl, pyridyl, pyrimidinyl, pyrrolyl, quinazolinyl, quinolinyl,quinoxalinyl, 1,2,3,4-tetrazolyl, thiazolinyl, thiazolyl, thienyl,1,2,3-triazinyl, 1,2,4-triazinyl, 1,3,5-triazinyl, 1,2,3-triazolyl, and1,2,4-triazolyl.

DETAILED DESCRIPTION OF THE INVENTION

The compounds of this invention have the following formula:

wherein:

(a) Ar₁ is

-   -   (1) furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl,        or    -   (2) substituted furanyl, substituted phenyl, substituted        pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or        substituted thienyl,        -   wherein said substituted furanyl, substituted phenyl,            substituted pyridazinyl, substituted pyridyl, substituted            pyrimidinyl, and substituted thienyl, have one or more            substituents independently selected from H, F, Cl, Br, I,            CN, NO₂, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl,            C₃-C₆ halocycloalkyl, C₃-C₆ cycloalkoxy, C₃-C₆            halocycloalkoxy, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₂-C₆            alkenyl, C₂-C₆ alkynyl, S(═O)_(n)(C₁-C₆ alkyl),            S(═O)_(n)(C₁-C₆ haloalkyl), OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆            haloalkyl), C(═O)NR_(x)R_(y), (C₁-C₆ alkyl)NR_(x)R_(y),            C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆            haloalkyl), C(═O)O(C₁-C₆ haloalkyl), C(═O)(C₃-C₆            cycloalkyl), C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl),            C(═O)O(C₂-C₆ alkenyl), (C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆            alkyl)S(C₁-C₆ alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆ alkyl),            phenyl, phenoxy, substituted phenyl, and substituted            phenoxy,        -   wherein such substituted phenyl and substituted phenoxy have            one or more substituents independently selected from H, F,            Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆            cycloalkyl, C₃-C₆ halocycloalkyl, C₃-C₆ cycloalkoxy, C₃-C₆            halocycloalkoxy, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₂-C₆            alkenyl, C₂-C₆ alkynyl, S(═O)_(n)(C₁-C₆ alkyl),            S(═O)_(n)(C₁-C₆ haloalkyl), OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆            haloalkyl), C(═O)NR_(x)R_(y), (C₁-C₆ alkyl)NR_(x)R_(y),            C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆            haloalkyl), C(═O)O(C₁-C₆ haloalkyl), C(═O)(C₃-C₆            cycloalkyl), C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl),            C(═O)O(C₂-C₆ alkenyl), (C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆            alkyl)S(C₁-C₆ alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆            alkyl)phenyl, and phenoxy;

(b) Het is a 5 or 6 membered, saturated or unsaturated, heterocyclicring, containing one or more heteroatoms independently selected fromnitrogen, sulfur, or oxygen, and where Ar₁ and Ar₂ are not ortho to eachother (but may be meta or para, such as, for a five membered ring theyare 1,3 and for a 6 membered ring they are either 1,3 or 1,4), and wheresaid heterocyclic ring may also be substituted with one or moresubstituents independently selected from H, OH, F, Cl, Br, I, CN, NO₂,oxo, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl, C₃-C₆halocycloalkyl, C₃-C₆ cycloalkoxy, C₃-C₆ halocycloalkoxy, C₁-C₆ alkoxy,C₁-C₆ haloalkoxy, C₂-C₆ alkenyl, C₂-C₆ alkynyl, S(═O)_(n)(C₁-C₆ alkyl),S(═O)_(n)(C₁-C₆ haloalkyl), OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆ haloalkyl),C(═O)NR_(x)R_(y), (C₁-C₆ alkyl)NR_(x)R_(y), C(═O)(C₁-C₆ alkyl),C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆ haloalkyl), C(═O)O(C₁-C₆ haloalkyl),C(═O)(C₃-C₆ cycloalkyl), C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl),C(═O)O(C₂-C₆ alkenyl), (C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆ alkyl), phenyl, phenoxy,substituted phenyl and substituted phenoxy

-   -   -   wherein such substituted phenyl and substituted phenoxy have            one or more substituents independently selected from H, F,            Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆            cycloalkyl, C₃-C₆ halocycloalkyl, C₃-C₆ cycloalkoxy, C₃-C₆            halocycloalkoxy, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₂-C₆            alkenyl, C₂-C₆ alkynyl, S(═O)_(n)(C₁-C₆ alkyl),            S(═O)_(n)(C₁-C₆ haloalkyl), OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆            haloalkyl), C(═O)H, C(═O)NR_(x)R_(y), (C₁-C₆            alkyl)NR_(x)R_(y), C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl),            C(═O)(C₁-C₆ haloalkyl), C(═O)O(C₁-C₆ haloalkyl), C(═O)(C₃-C₆            cycloalkyl), C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl),            C(═O)O(C₂-C₆ alkenyl), (C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆            alkyl)S(C₁-C₆ alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆ alkyl),            phenyl, and phenoxy;

(c) Ar₂ is

-   -   (1) furanyl, phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl,        or    -   (2) substituted furanyl, substituted phenyl, substituted        pyridazinyl, substituted pyridyl, substituted pyrimidinyl, or        substituted thienyl,        -   wherein said substituted furanyl, substituted phenyl,            substituted pyridazinyl, substituted pyridyl, substituted            pyrimidinyl, and substituted thienyl, have one or more            substituents independently selected from H, F, Cl, Br, I,            CN, NO₂, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl,            C₃-C₆ halocycloalkyl, C₃-C₆ cycloalkoxy, C₃-C₆            halocycloalkoxy, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₂-C₆            alkenyl, C₂-C₆ alkynyl, S(═O)_(n)(C₁-C₆ alkyl),            S(═O)_(n)(C₁-C₆ haloalkyl), OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆            haloalkyl), C(═O)NR_(x)R_(y), (C₁-C₆ alkyl)NR_(x)R_(y),            C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆            haloalkyl), C(═O)O(C₁-C₆ haloalkyl), C(═O)(C₃-C₆            cycloalkyl), C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl),            C(═O)O(C₂-C₆ alkenyl), (C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆            alkyl)S(C₁-C₆ alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆ alkyl),            phenyl, phenoxy, substituted phenyl and substituted phenoxy        -   wherein such substituted phenyl and substituted phenoxy have            one or more substituents independently selected from H, F,            Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆            cycloalkyl, C₃-C₆ halocycloalkyl, C₃-C₆ hydroxycycloalkyl,            C₃-C₆ cycloalkoxy, C₃-C₆ halocycloalkoxy, C₁-C₆ alkoxy,            C₁-C₆ haloalkoxy, C₂-C₆ alkenyl, C₂-C₆ alkynyl,            S(═O)_(n)(C₁-C₆ alkyl), S(═O)_(n)(C₁-C₆ haloalkyl),            OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆ haloalkyl), C(═O)H,            C(═O)NR_(x)R_(y), (C₁-C₆ alkyl)NR_(x)R_(y), C(═O)(C₁-C₆            alkyl), C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆ haloalkyl),            C(═O)O(C₁-C₆ haloalkyl), C(═O)(C₃-C₆ cycloalkyl),            C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₁-C₆ haloalkyl),            C(═O)(C₂-C₆ alkenyl), C(═O)O(C₂-C₆ alkenyl), (C₁-C₆            alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆ alkyl),            C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆ alkyl), phenyl, and phenoxy);

(d) X is 0 or S;

(e) R1 is selected from H, CN, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆cycloalkyl, C₃-C₆ halocycloalkyl, C₃-C₆ cycloalkoxy, C₃-C₆halocycloalkoxy, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₂-C₆ alkenyl, C₂-C₆alkynyl, S(═O)_(n)(C₁-C₆ alkyl), S(═O)_(n)(C₁-C₆ haloalkyl), OSO₂(C₁-C₆alkyl), OSO₂(C₁-C₆ haloalkyl), C(═O)NR_(x)R_(y), (C₁-C₆alkyl)NR_(x)R_(y), C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆haloalkyl), C(═O)O(C₁-C₆ haloalkyl), C(═O)(C₃-C₆ cycloalkyl),C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl), C(═O)O(C₂-C₆ alkenyl),(C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆ alkyl), C(═O)(C₁-C₆alkyl)C(═O)O(C₁-C₆ alkyl), phenyl, phenoxy;

(f) R2, R3 and R4 are independently selected from H, C₁-C₆ alkyl, C₃-C₆cycloalkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, C(═O)(C₁-C₆ alkyl),C(═O)O(C₁-C₆ alkyl), C(═O)(C₃-C₆ cycloalkyl), C(═O)O(C₃-C₆ cycloalkyl),C(═O)(C₂-C₆ alkenyl), C(═O)O(C₂-C₆ alkenyl), (C₁-C₆ alkyl)O(C₁-C₆alkyl), (C₁-C₆ alkyl)S(C₁-C₆ alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆alkyl), C(═O)phenyl, phenyl, C₁-C₆ alkylphenyl, C₁-C₆ alkylphenoxy,indanyl, C(═O)Het-1, Het-1, (C₁-C₆ alkyl)Het-1, or C₁-C₆ alkyl-O-Het-1,

wherein each alkyl, cycloalkyl, cycloalkoxy, halocycloalkoxy, alkoxy,haloalkoxy, alkenyl, alkynyl, C₁-C₆ alkylphenyl, phenyl, phenoxy, andHet-1, are optionally substituted with one or more substituentsindependently selected from F, Cl, Br, I, CN, NO₂, NR_(x)R_(y), C₁-C₆alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl, C₃-C₆ halocycloalkyl, C₃-C₆cycloalkoxy, C₃-C₆ halocycloalkoxy, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy,C₂-C₆ alkenyl, C₃-C₆ cycloalkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkynyl,S(═O)_(n)(C₁-C₆ alkyl), S(═O)_(n)(C₁-C₆ haloalkyl), S(═O)₂N(C₁-C₆alkyl)₂, OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆ haloalkyl), C(═O)H,C(═O)NR_(x)R_(y), (C₁-C₆ alkyl)NR_(x)R_(y), C(═O)(C₁-C₆ alkyl),C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆ haloalkyl), C(═O)O(C₁-C₆ haloalkyl),C(═O)(C₃-C₆ cycloalkyl), C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl),C(═O)O(C₂-C₆ alkenyl), (C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆ alkyl), phenyl, phenoxy, O-Het-1,and Het-1,

-   -   wherein Het-1 is a 5- or 6-membered, saturated or unsaturated,        heterocyclic ring, containing one or more heteroatoms        independently selected from nitrogen, sulfur or oxygen,

wherein R3 and R4 together can optionally form a 3- to 8-memberedsaturated or unsaturated cyclic group which may contain one or moreheteroatoms selected from nitrogen, sulfur, and oxygen;

(g) n=0, 1, or 2;

(h) R_(x) and R_(y) are independently selected from H, C₁-C₆ alkyl,C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl, C₃-C₆ halocycloalkyl, C₂-C₆ alkenyl,C₂-C₆ alkynyl, S(═O)_(n)(C₁-C₆ alkyl), S(═O)_(n)(C₁-C₆ haloalkyl),OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆ haloalkyl), C(═O)H, C(═O)(C₁-C₆ alkyl),C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆ haloalkyl), C(═O)O(C₁-C₆ haloalkyl),C(═O)(C₃-C₆ cycloalkyl), C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl),C(═O)O(C₂-C₆ alkenyl), (C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆ alkyl), and phenyl.

In another embodiment An is a substituted phenyl wherein saidsubstituted phenyl, has one or more substituents independently selectedfrom C₁-C₆ alkyl, C₁-C₆ haloalkyl, and C₁-C₆ haloalkoxy. In a morepreferred embodiment An is a substituted phenyl wherein said substitutedphenyl, has one or more substituents independently selected from OCF₃,OCF₂CF₃, CF₃,

In another embodiment Het is a triazolyl, imidazolyl, pyrrolyl, orpyrazolyl.

In another embodiment Het is a substituted pyrazolyl wherein saidsubstituted pyrazolyl has one or more substituents independentlyselected from H, C(═O)O(C₁-C₆ alkyl), or C(═O)NR_(x)R_(y).

In another embodiment Ar₂ is a phenyl.

In another embodiment R1 is an H or a C₁-C₆ alkyl.

In another embodiment R2 is H or a C₁-C₆ alkyl.

In another embodiment R3 is H.

In another embodiment X is S.

In another embodiment R4 is a C₁-C₆ alkyl, C₃-C₆ cycloalkyl, C₂-C₆alkenyl, C(═O)phenyl, C₁-C₆ alkylphenyl, Het-1, or (C₁-C₆ alkyl)Het-1.

In another embodiment R4 is a C₁-C₆ alkyl, C₁-C₆ alkylphenyl, phenyl, orHet-1, wherein each is substituted with one or more substituentsindependently selected from F, Cl, Br, I, CN, NO₂, NR_(x)R_(y), C₁-C₆alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₃-C₆cycloalkenyl, S(═O)_(n)(C₁-C₆ alkyl), S(═O)_(n)(C₁-C₆ haloalkyl),S(═O)₂N(C₁-C₆ alkyl)₂, C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl),C(═O)(C₁-C₆ haloalkyl), (C₁-C₆ alkyl)O(C₁-C₆ alkyl), phenyl, O-Het-1,and Het-1.

While these embodiments have been expressed, other embodiments andcombinations of these expressed embodiments and other embodiments arepossible.

Preparation of Triaryl-Intermediates

Compounds of this invention can be prepared by making a triarylintermediate, Ar₁-Het-Ar₂, and then linking it to the desiredintermediate to form the desired compound. A wide variety of triarylintermediates can be used to prepare compounds of this invention,provided that such triaryl intermediates contain a suitable functionalgroup on Ar₂ to which the rest of the desired intermediate can beattached. Suitable functional groups include an oxoalkyl, or formylgroup. These triaryl intermediates can be prepared by methods previouslydescribed in the chemical literature. Several of these methods aredescribed below.

Intermediates wherein ‘Het’ is a disubstituted pyridine, pyrimidine,pyrazine or pyridizine can be made by coupling of a halo- oralkylthio-substituted pyridine, pyrimidine or pyrazine with an arylboronic acid or borate ester, under Suzuki arylation conditions. See,for example, the following.

For pyridines: Couve-Bonnaire et al. Tetrahedron 2003, 59, 2793 andPuglisi et al. Eur. J. Org. Chem. 2003, 1552.

For pyrazines: Schultheiss and Bosch Heterocycles 2003, 60, 1891.

For pyrimidines: Qing et al. J. Fluorine Chem. 2003, 120, 21 and Ceideand Montalban Tetrahedron Lett. 2006, 47, 4415.

For 2,4-diaryl pyrimidines: Schomaker and Delia, J. Org.Chem. 2001, 66,7125.

Thus, successive palladium-catalyzed arylations, using 4-formylphenylboronic acid and 4-trifluoromethoxyphenyl boronic acid, can generatevirtually any particular substitution pattern, as shown in the schemebelow:

Similarly, diaryl pyridines and pyrazines and other dihalogenatedheterocyclic aromatic compounds can be prepared from dihalogenatedpyridines and pyrazines and other dihalogenated heterocyclic aromaticcompounds using the same protocol:

The halo- or alkylthio-pyrimidine and pyridine precursors are eithercommercially available, or may be synthesized by routes described in theliterature (Rorig and Wagner U.S. Pat. No. 3,149,109, 1964; Kreutzbergerand Tesch Arzneim.-Forsch. 1978, 28, 235).

Intermediate compounds wherein ‘Het’ is a 1,3-disusbstituted1,2,4-triazole can be prepared according to one of the followingschemes.

Route A: 1,3-Diaryl 1,2,4-triazoles were prepared from the corresponding—NH 3-aryl 1,2,4-triazoles by following a published route forN-arylation of imidazoles (Lin et al. J. Org. Chem. 1979, 44, 4160).Coupling of 1,2,4-triazoles to aryl halides was done under thermal or,preferably, microwave conditions (Antilla et al. J. Org. Chem. 2004, 69,5578). (DIBAL is diisobutylaluminum hydride.)

Route B: Bromination of hydrazones followed by treatment of thebromohydrazone with tetrazole results in formation of the 1,3-diaryl1,2,4-triazole (Butler and Fitzgerald J. Chem. Soc., Perkin Trans. I1988, 1587).

Compounds where ‘Het’ is an imidazole can be prepared according to oneof the following schemes:

Route A (Step 1: Lynch et al. J. Am. Chem. Soc. 1994, 116, 11030. Step2: Liu et al. J. Org. Chem. 2005, 70, 10135):

Route B. For halo-aryl groups that also contain an activating group suchas nitro or cyano, displacement of an aryl halide with an imidazole,using a base such as potassium carbonate in a polar aprotic solvent,such as N,N-dimethylformamide (DMF) or dimethyl sulfoxide (DMSO), can beaccomplished in the following manner (Bouchet et al. Tetrahedron 1979,35, 1331):

Route C: Following a procedure first described by Porretta et al.(Farmaco, Edizione Scientifica 1985, 40, 404), an N-phenacyl aniline istreated with potassium thiocyanate in acidic medium (HCl), and theresulting 2-mercapto imidazole is then converted into the desulfurizeddiaryl imidazole by treatment with nitric acid in acetic acid.

Route D. N-Arylation of 4-bromoimidazole under microwave irradiationconditions (Route A, Step 2) furnished the intermediate1-aryl-4-bromoimidazole, which was converted into triaryl-intermediatesby treatment with aryl boronic acids under palladium-catalyzedconditions.

Compounds where ‘Het’ is a 1,4-disubstituted 1,2,3-triazole can beprepared according to the following scheme (Feldman et al. Org Lett.2004, 6, 3897):

Compounds where ‘Het’ is a 3,5-disubstituted 1,2,4-triazole can beprepared according to the following scheme (Yeung et al. TetrahedronLett. 2005, 46, 3429):

Compounds where ‘Het’ is a 1,3-disubstituted 1,2,4-triazolin-5-one canbe prepared according to the following scheme (Pirrung and Tepper J.Org. Chem. 1995, 60, 2461 and Lyga Synth. Commun. 1986, 16, 163). (DPPAis diphenyl phosphoryl azide.):

Compounds where ‘Het’ is a 1,3-diaryl pyrazoline can be preparedaccording to the following scheme. The monohydrazone ofterephthalaldehyde is treated with N-chlorosuccinimide (NCS) inisopropyl alcohol (i-PrOH), and the resulting chlorohydrazoneintermediate is treated directly with base and a substituted olefin togenerate the pyrazoline:

Compounds where ‘Het’ is a 3,5-disubstituted isoxazole can be preparedaccording to the following scheme:

Compounds where ‘Het’ is a 1,3-disubstituted pyrazole can be preparedaccording to the following scheme. Coupling of the pyrazole tohalogenated aromatics was accomplished using microwave conditionsdescribed by Liu et al., Route A, Step 2 above. (DMA is dimethylacetal.)

Compounds where ‘Het’ is a 1,4-disubstituted pyrazole can be preparedaccording to the following scheme. 4- Bromopyrazole is first coupledwith an iodophenyl analog, and the resulting 1-aryl-4-bromopyrazole isthen coupled with a phenylboronic acid using conditions describedearlier for arylation of imidazoles.

Compounds where ‘Het’ is a 2,4-disubstituted thiazole are prepared bycondensation of a thioamide to an α-halo acetophenone in a proticsolvent such as ethanol (for example, Potts and Marshall J. Org. Chem.1976, 41, 129).

Compounds where ‘Het’ is a 2,4-disubstituted oxazoline are preparedstarting from the α-bromoacetophenone according to the following scheme(Periasamy et al. Synthesis 2003, 1965 and Liu et al. J. Am. Chem. Soc.2007, 129, 5834).

Compounds where ‘Het’ is a 2,5-disubstituted oxazoline are preparedaccording to the following scheme (Favretto et al. Tetrahedron Lett.2002, 43, 2581 and Liu et al. J. Am. Chem. Soc. 2007, 129, 5834):

Compounds where ‘Het’ is a 3,5-disubstituted 1,2,4-triazine are preparedaccording to the following scheme (Reid et al. Bioorg. Med. Chem. Lett.2008, 18, 2455 and Saraswathi and Srinivasan Tetrahedron Lett. 1971,2315):

Preparation of Hydrazone-Linked Compounds

Hydrazone-linked compounds can be prepared from the corresponding arylaldehydes or ketones by one of three methods: (A) by reaction withhydrazine, followed by reaction with an aryl isothiocyanate intetrahydrofuran (THF), at temperatures between 0 and 100° C.; (B) byreaction with methyl hydrazinecarbodithioate, followed by reaction withan amine in a polar aprotic solvent such as DMF, at temperatures between25 and 150° C.; or (C) by reaction with an alkyl or aryl semicarbazideor thiosemicarbazide, that is either commercially available or can beprepared by one who is skilled in the art, in a polar protic solventsuch as ethyl alcohol (EtOH), at temperatures between 0 and 100° C.

EXAMPLES

The examples are for illustration purposes and are not to be construedas limiting the invention disclosed in this document to only theembodiments disclosed in these examples.

Starting materials, reagents and solvents which were obtained fromcommercial sources were used without further purification. Anhydroussolvents were purchased as Sure/Seal™ from Aldrich and were used asreceived. Melting points were obtained on a Thomas Hoover Unimeltcapillary melting point apparatus or an OptiMelt Automated Melting PointSystem from Sanford Research Systems and are uncorrected.

Example 1 Preparation of4-[1-(4-trifluoromethoxyphenyl)-1H-pyrrol-3-yl]-benzaldehyde

Step 1. 1-(4-Trifluoromethoxyphenyl)-1H-pyrrole. The compound wasprepared according to Colotta et al. J. Med. Chem. 2006, 49, 6015. Asolution of 4-trifluoromethoxyphenyl amine (500 milligrams (mg), 2.82millimoles (mmol), 1.00 equivalent (eq)) and 2,5-diethoxytetrahydrofuran (452 mg, 2.82 mmol, 1.00 eq) in glacial acetic acid (20milliliters (mL)) was heated at 90° C. for 1 hour (h) before being driedonto silica gel. The residue was then slurried in refluxing hexane,filtered hot, and concentrated to dryness affording the desiredintermediate (519 mg, 81%).

Step 2. 3-Bromo-1-(4-trifluoromethoxyphenyl)-1H-pyrrole. The compoundwas prepared according to Bray et al. J. Org. Chem. 1990, 55, 6317. To asolution of 1-(4-trifluoromethoxyphenyl)-1H-pyrrole (519 mg, 2.29 mmol,1.00 eq) in THF (250 mL) at −78° C. was added a 0.05 M solution ofN-bromosuccinimide (NBS; 408 mg, 2.29 mmol, 1.00 eq) in THF over 45minutes (min). The vessel was slowly warmed to room temperature beforeconcentration to afford the crude bromopyrrole, which was shown toconsist of 55% desired intermediate by GC-MS. The material was used inthe subsequent reaction without further purification.

Step 3. 4-[1-(4-Trifluoromethoxyphenyl)-1H-pyrrol-3-yl]-benzaldehyde. Asuspension of crude 3-bromo-1-(4-trifluoromethoxyphenyl)-1H-pyrrole (356mg, 1.26 mmol, 1.00 eq), 4-formylphenylboronic acid (283 mg, 1.89 mmol,1.50 eq), bis(triphenylphosphine)palladium(II) dichloride (27 mg, 0.04mmol, 0.03 eq), 2 M Na₂CO₃ (aq) (1.26 mL, 2.52 mmol, 2.0 eq), and1,4-dioxane (5 mL) were heated at 150° C. in a microwave reaction vesselfor 45 min. The cooled solution was then diluted with EtOAc (20 mL),filtered over Celite®, concentrated to dryness, and purified viachromatography (2:2:1, hexane:EtOAc:acetone) to afford the desiredintermediate (79 mg, 21%).

Example 2 Preparation of4-[1-(4-trifluoromethoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl]-benzaldehyde

Step 1. 1-(4-Trifluoromethoxyphenyl)-pyrazolidin-3-one: The compound wasprepared according to Rees and Tsoi Chem. Commun. 2000, 415. Asuspension of (4-trifluoromethoxyphenyl)-hydrazine hydrochloride (300mg, 1.32 mmol, 1.00 eq), 3-chloropropionyl chloride (167 mg, 1.32 mmol,1.00 eq), and PS-DIEA (1.30 grams (g), 5.28 mmol, 4.00 eq) in THF (20mL) was stirred at ambient temperature for 12 h. The solution was thenfiltered, concentrated to dryness, and purified via chromatography(2:2:1, hexane:EtOAc:acetone) to afford the desired intermediate (120mg, 37%).

Step 2. 3-Chloro-1-(4-trifluoromethoxyphenyl)-4,5-dihydro-1H-pyrazole:The general procedure was taken from Wang et al. Tetrahedron Lett. 2005,46, 2631. To a solution of1-(4-trifluoromethoxyphenyl)-pyrazolidin-3-one (120 mg, 0.49 mmol, 1.00eq) in toluene (20 mL) was slowly added phosphoryl chloride (22.5 mg,1.47 mmol, 3.00 eq). The mixture was then heated at 80° C. for 1 hbefore cooling to room temperature and quenching with H₂O (10 mL). Thevessel was stirred under an atmosphere of nitrogen (N₂) for 8 h beforethe product was extracted into EtOAc (200 mL), dried (MgSO₄), andconcentrated under reduced pressure. GC-MS proved 88% formation of thedesired intermediate, which was used in subsequent reactions withoutfurther purification.

Step 3.4-[1-(4-Trifluoromethoxyphenyl)-4,5-dihydro-1H-pyrazol-3-yl]-benzaldehye:A suspension of3-chloro-1-(4-trifluoromethoxyphenyl)-4,5-dihydro-1H-pyrazole (114 mg,0.43 mmol, 1.00 eq), 4-formylphenylboronic acid (97 mg, 0.65 mmol, 1.50eq), bis(triphenylphosphine)palladium(II) dichloride (10 mg, 0.01 mmol,0.03 eq), 2 M Na₂CO₃ (aq) (0.43 mL, 0.86 mmol, 2.0 eq), and 1,4-dioxane(5 mL) were heated at 150° C. in a microwave reaction vessel for 45 min.The cooled solution was then diluted with EtOAc (20 mL), filtered overCelite®, concentrated to dryness, and purified via chromatography(2:2:1, hexane:EtOAc:acetone) to afford the desired intermediate (50 mg,0.15 mmol, 31%).

Example 3 Preparation of4-[1-(4-trifluoromethoxyphenyl)-1H-pyrazol-4-yl]-benzaldehyde

Step 1. 4-Bromo-1-(4-trifluoromethoxyphenyl)-1H-pyrazole.4-Bromopyrazole (1.5 g, 10 mmol) and 4-iodotrifluoromethoxybenzene (3.0g, 10.3 mmol) were stirred DMF (8 mL) and treated with potassiumphosphate (6.3 g, 30 mmol) and CuI (0.5 g, 2.6 mmol). The solution wasstirred and heated to 130° C. for 30 min, then it was cooled to ambienttemperature and poured into 1 N NH₄OH (50 mL). The solid precipitate wasisolated by filtration, re-dissolved in ether, filtered and concentratedto a tan solid. Recrystallization from EtOH gave an off-white solid (2.1g): mp 63-65° C.; LCMS 308.6 (M+1).

Step 2. 4-[1-(4-Trifluoromethoxyphenyl)-1H-pyrazol-4-yl]-benzaldehyde. Asuspension of the bromopyrazole (0.31 g, 1 mmol) and 4-formylboronicacid (0.15 g, 1 mmol), 2 M aqueous potassium carbonate solution (1 mL),and tetrakis(triphenylphosphine)-palladium(0) (35 mg, cat) in dioxane (6mL) was heated to 150° C. in a microwave reactor. The residue was thenconcentrated in vacuo and purified by chromatography (0-100%EtOAc-hexanes) to give the title compound (175 mg) as a tan solid: mp107-109° C.; LCMS 332.8 (M+1).

Example 4 Preparation of4-[5-(4-propylphenyl)-isoxazol-3-yl]-benzaldehyde

Step 1. 4-(Hydroxyiminomethyl)-benzonitrile. The compound was preparedaccording to Biasotti et al. Bioorg. Med. Chem. 2003, 11, 2247. Asuspension of 4-formylbenzonitrile (500 mg, 3.81 mmol, 1.00 eq),hydroxylamine hydrochloride (290 mg, 4.19 mmol, 1.10 eq), and sodiumacetate (1.56 g, 19.05 mmol, 5.00 eq) in MeOH (50 mL) was heated at 70°C. for 4 h before concentration to dryness. The residue was thenslurried in Et₂O, filtered, and concentrated to afford the desiredintermediate (496 mg, 3.39 mmol, 89%).

Step 2. 4-(Hydroxyimino-bromomethyl)-benzonitrile. The compound wasprepared according to Tanaka et al. Bull. Chem. Soc. Jpn. 1984, 57,2184. A 0.05 M solution of N-bromosuccinimide (724 mg, 4.07 mmol, 1.20eq) in CH₂Cl₂ was added dropwise to a 0° C. solution of4-(hydroxyiminomethyl)-benzonitrile (496 mg, 3.39 mmol, 1.00 eq) inCH₂Cl₂ (50 mL). The solution was warmed to room temperature before beingvolumetrically partitioned between two different reaction vials. Eachvial was then concentrated and the crude residues were used withoutfurther purification.

Step 3. 4-[5-(4-Propylphenyl)-isoxazol-3-yl]-benzonitrile. A solution of4-(hydroxyimino-bromomethyl)-benzonitrile (381 mg, 1.70 mmol),triethylamine (0.71 mL, 5.10 mmol, 3.0 eq), and1-ethynyl-4-propylbenzene (1.23 g, 8.50 mmol, 5.0 eq) in toluene (20 mL)was heated at 100° C. for 1 h before concentration to dryness.Purification via normal phase chromatography afforded the desiredintermediate (108 mg, 22%). Reduction of the nitrile to thecorresponding aldehyde was accomplished following the DIBAL proceduredescribed earlier.

Example 5 Preparation of4-{1-[4-(1-hydroxypropyl)-phenyl]-1H-pyrazol-3-yl}-benzaldehyde

Step 1. 3-(4-Cyanophenyl)pyrazole. To a round bottom flask equipped withmechanical stir bar and reflux condenser were added p-cyanoacetophenone(5 g, 34.44 mmol) and dimethylformamide dimethylacetal (DMF-DMA; 40 mL).The mixture was stirred at reflux for 5 h before concentration underreduced pressure afforded the crude dimethylamino-acryloylbenzonitrileintermediate. The residue was then suspended in a minimal volume of EtOH(˜20 mL), charged with hydrazine monohydrate (1.67 mL, 34.4 mmol), andheated at 80° C. for 30 min before concentration. The crude3-(4-cyanophenyl)pyrazole material (5.59 g, 33 mmol, 96%) which wasisolated was of sufficient purity for use in the subsequent reaction.

Step 2. 4-[1-(4-Propionyl-phenyl)-1H-pyrazol-3-yl]-benzonitrile.4-(1H-Pyrazol-3-yl)-benzonitrile (100 mg, 0.591 mmol),1-(4-bromophenyl)-propan-1-one (126 mg, 0.591 mmol), Cs₂CO₃ (770 mg,2.364 mmol), CuI (4 mg, 0.018 mmol), 8-hydroxyquinoline (3 mg, 0.018mmol), and DMF/H₂O (2 mL; 10:1 solution) were combined in a 10 mL CEMMicrowave reaction vessel fitted with magnetic stir bar and subjected tomicrowave irradiation at 150° C. for 30 min. The contents were thenfiltered and concentrated to dryness affording the nitrile (158 mg,0.508 mmol, 86%). Reduction of the nitrile to the corresponding aldehydewas accomplished following the DIBAL procedure described earlier.

Example 6 Preparation of5-(4-formylphenyl)-2-(4-trifluoromethoxyphenyl)-3,4-dihydro-2H-pyrazole-3,4-dicarboxylicacid diethyl ester

Step 1. Preparation of4-[(4-trifluoromethoxyphenyl)-hydrazonomethyl]-benzaldehyde. Thecompound was prepared according to Paulvannan et al. Tetrahedron 2000,56, 8071. To a stirred solution of benzene-1,4-dicarbaldehyde (1.50 g,11.2 mmol, 1.0 eq) in i-PrOH (250 mL) was added4-trifluoromethoxyphenylhydrazine hydrochloride (2.55 g, 11.2 mmol, 1.0eq) portionwise over 5 min. The solution was stirred at ambienttemperature for 1 h before concentration to dryness and purification viachromatography (2:2:1 hexane:EtOAc:acetone) to afford the intermediate(2.48 g, 72%).

Step 2. Chlorohydrazone synthesis. The intermediate was preparedaccording to Lokanatha Rai and Hassner Synth. Commun. 1989, 19, 2799. Asolution of 44(4-trifluoromethoxyphenyl)-hydrazonomethyl]-benzaldehyde(2.48 g, 8.05 mmol, 1.00 eq) and N-chlorosuccinimide (1.61 g, 12.08mmol, 1.5 eq) in i-PrOH (100 mL) was heated at 80° C. for 1 h. Thesolution was then cooled and volumetrically partitioned evenly betweensix different reaction vessels to each contain 1.34 mmol of theintermediate.

Step 3. Pyrazoline synthesis. The compounds were prepared according toPaulvannan et al. Tetrahedron 2000, 56, 8071. To each reaction vesselwere added triethylamine (0.56 mL, 4.02 mmol, 3.00 eq) and therespective acrylates (6.70 mmol, 5.00 eq). The reaction mixtures werethen heated at 70° C. for 90 min before concentration to dryness andpurification via chromatography (2:2:1, hexane:EtOAc:acetone). Reductionof the nitriles to the corresponding aldehydes was accomplishedfollowing the DIBAL procedure described earlier.

Example 7 Preparation of4-{1-[4-(2,2,2-trifluoroethoxy)-phenyl]-1H-imidazol-4-yl}-benzaldehyde

4-(2-Bromoacetyl)-benzonitrile (58 mg, 0.21 mmol) and4-(2,2,2-trifluoroethoxy)-phenylamine (50 mg, 0.21 mmol) were combinedin a 100 mL Erlenmeyer flask fitted with a magnetic stir bar. Thecontents were dissolved in EtOH (1 mL) and stirred at ambienttemperature for 2 h. The crude intermediate was then transferred to a100 mL round bottom flask containing KSCN (21 mg, 0.21 mmol) and conc.HCl (18 μL, 0.21 mmol). The vessel was heated at 80° C. for 1 h beforeits contents were poured into 1:1 H₂O/NH₄OH solution (5 mL). Thesolution was allowed to stand for 24 h, and then the solid was filteredand washed with ether to afford the intermediate imidazolethiol (32 mg,0.086 mmol, 33%). An aqueous solution of HNO₃ (1.35 mL, 0.387 mmol) andKNO₃ (1 mg, 0.003 mmol) was then added dropwise over 10 min to asuspension of the imidazolethiol in acetic acid (2 mL). After stirringfor 2 h at ambient temperature the solution was poured into crushed iceand neutralized (pH=7) with 0.1 N sodium hydroxide (NaOH, aq). Theintermediate nitrile was isolated by vacuum filtration and dried in a45° C. vacuum oven for 12 h (23 mg, 78%), mp 179° C. Reduction to thecorresponding aldehyde was accomplished using DIBAL under conditionsdescribed previously.

Example 8 Preparation of4-[1-(4-propylphenyl)-1H-imidazol-4-yl]-benzaldehyde

4-Propylaniline (2.70 g, 20 mmol) was added dropwise to a solution of4-cyanophenacyl bromide (2.20 g, 10 mmol) in DMF (5 mL). This solutionwas then added to hot (180° C.) formamide (20 mL) over 5 min, and thecombined solution was allowed to stir at 180° C. for 2 h. The cooledsolution was then poured onto ice (100 mL), and extracted with ether(2×75 mL). After drying and concentrating, the resulting dark oil waspurified by chromatography (3:1:2 hexanes:EtOAc:CH₂Cl₂). The firstproduct (510 mg) was identified as4-(5-propyl-1H-indol-3-yl)-benzonitrile, mp 140° C. The second fraction(275 mg) was identified as the desired imidazole: mp 133° C.; ¹H NMR(400 MHz, CDCl₃) δ 7.95 (d, J=6 Hz, 2H), 7.90 (s, 1H), 7.70 (d, J=6 Hz,2H), 7.68 (s, 1H), 7.38 (d, J=4 Hz, 2H), 7.31 (d, J=4 Hz, 2H), 2.69 (t,J=8.9 Hz, 2H), 1.68 (m, 2H), 0.98 (t, J=7.5 Hz, 3H); ESIMS m/z 288.1(M+H).

Reduction to the corresponding aldehyde was accomplished using DIBALunder conditions described previously: mp 97° C.; ¹H NMR (300 MHz,CDCl₃) δ 10.02 (s, 1H), 8.03 (d, J=6 Hz, 2H), 7.92 (d, J=6 Hz, 2H), 7.90(s, 1H), 7.72 (s, 1H), 7.38 (d, J=4 Hz, 2H), 7.31 (d, J=4 Hz, 2H), 2.69(t, J=8.9 Hz, 2H), 1.68 (m, 2H), 0.98 (t, J=7.5 Hz, 3H); ESIMS m/z 291.1(M+H).

Example 9 Preparation of4-[1-(4-trifluoromethoxyphenyl)-1H-imidazol-4-yl]-benzaldehyde

4-Trifluoromethoxyaniline (2.20 g, 12.4 mmol) was added dropwise to asolution of 4-cyanophenacyl bromide (1.50 g, 6.7 mmol) in DMF (5 mL).This solution was then added to hot (180° C.) formamide (20 mL) over 5min, and the combined solution was allowed to stir at 180° C. for 2 h.The cooled solution was then poured onto ice (100 mL), and extractedwith ether (2×75 mL). After drying and concentrating, the resultingsemi-solid was crystallized from MeOH/H₂O. A second recrystallizationfrom MeOH/H₂O removed traces of the formanilide impurity and furnishedpure product (200 mg): mp 155° C. Anal. Calcd. for C₁₇H₁₀F₃N₃O: C,62.01; H, 3.06; N, 12.76. Found: C. 61.53; H, 3.13; N, 12.55. Reductionto the corresponding aldehyde was accomplished using DIBAL underconditions described previously: mp 112° C.; ¹H NMR (300 MHz, CDCl₃) δ10.0 (s, 1H), 8.05-7.90 (m, 5H), 7.70 (s, 1H), 7.50 (d, J=6 Hz, 2H),7.42 (d, J=6 Hz, 2H); ESIMS m/z 333.0 (M+H).

Example 10 Preparation of4-[4-(4-trifluoromethylphenyl)-1H-imidazol-1-yl]-benzaldehyde

4-Trifluoromethylphenyl imidazole (4.0 g, 19 mmol), 4-fluorobenzonitrile(1.2 g, 8.5 mmol) and potassium carbonate (1.5 g, 10.9 mmol) werecombined in DMSO (15 mL) and heated at 100° C. for 6 h. The cooledsolution was then poured onto water (H₂O; 100 mL), and the resultingsolid was filtered and air-dried to give the imidazole nitrile (4.65 g)as a white solid: mp 252° C.; ¹H NMR (300 MHz, CDCl₃) δ 8.05 (s, 1H),7.95 (d, J=8 Hz, 2H), 7.85 (d, J=8 Hz, 2H), 7.72 (s, 1H), 7.72 (d, J=8Hz, 2H), 7.62 (d, J=8 Hz, 2H); ESIMS m/z 314.1 (M+H). Anal. Calcd. forC₁₆H₁₀F₃N₃O₂: C, 65.18; H, 3.22; N, 13.41. Found: C, 64.49; H, 3.23; N,13.08. A portion of the nitrile (3.8 g) was reduced in the presence ofDIBAL under conditions described previously to give the correspondingaldehyde (2.41 g): mp 141° C.; ¹H NMR (300 MHz, CDCl₃) δ 10.1 (s, 1H),8.10 (d, J=8 Hz, 2H), 8.05 (s, 1H), 7.95 (d, J=8 Hz, 2H), 7.75 (s, 1H),7.7 (m, 4H); ESIMS m/z 317.1 (M+H).

Example 11 Preparation of4-bromo-1-(4-trifluoromethoxyphenyl)-1H-imidazole

A round bottom flask was charged with 4-bromoimidazole (1.15 g, 7.81mmol), CuI (0.07 g, 0.36 mmol), 8-hydroxyquinoline (0.05 g, 0.36 mmol),cesium carbonate (3.39 g, 10.4 mmol) and 4-trifluoromethoxyiodobenzene(1.50 g, 5.21 mmol). A 10:1 mixture of DMF (15 mL) and H₂O (1.5 mL) wasadded to the reaction mixture, and the solution was heated to 130° C.for 4 h. The reaction mixture was then diluted with EtOAc and washedsequentially with H₂O, ammonium chloride (NH₄Cl, saturated), H₂O andsodium bicarbonate (NaHCO₃). The organics were dried over MgSO₄,filtered and purified by reverse phase column chromatography to give theimidazole (820 mg) as a white solid: mp 139-141° C.; ESIMS m/z 308.0(M+H).

Example 12 Preparation of 4-methoxy-2-[1-(4-trifluoromethoxyphenyl)-1H-imidazol-4-yl]-benzaldehyde

4-Bromo-1-(4-trifluoromethoxyphenyl)-1H-imidazole (100 mg, 0.326 mmol),2-formyl-5-methoxyphenylboronic acid (73 mg, 0.41 mmol),bis(triphenylphosphine)palladium dichloride (2 mg, 0.003 mmol), NaHCO₃(49 mg, 0.59 mmol) and 1:1 DME/H₂O (8:8 mL) were combined and added to amicrowave vessel. The reaction mixture was heated in the microwave withstirring at 100° C. for 12 min. The microwave took 5 min to reach 100°C., then maintained at 100° C. for 12 min, and then cooled. TLC (1:1EtOAc:cyclohexane) showed the presence of starting materials, thus thesample was heated to 100° C. for another 8 min. Upon cooling aprecipitate formed; this was filtered and washed with H₂O to give a greysolid (86 mg): ESIMS m/z 363.0 (M+H).

The following intermediate was also prepared using this procedure:

Example 13 Preparation of2-fluoro-4-[1-(4-trifluoromethoxyphenyl)-1H-imidazol-4-yl]-benzaldehyde

ESIMS m/z 351.0 (M+H).

Example 14 Preparation of1-{4-fluoro-3-[1-(4-trifluoromethoxyphenyl)-1H-imidazol-4-yl]-phenyl}-ethanone

4-Bromo-1-(4-trifluoromethoxyphenyl)-1H-imidazole (200 mg, 0.651 mmol),5-acetyl-2-fluorophenylboronic acid (178 mg, 0.977 mmol),tetrakis(triphenylphosphine)-palladium(0) (7 mg, 0.007 mmol), a 2 Naqueous solution of potassium carbonate (0.651 mL) and dioxane (8 mL)were combined and added to a microwave vessel. The reaction mixture washeated in the microwave with stirring to 150° C. for 20 min. LC-MSindicated 88% anticipated product; TLC (1:1 hexanes:EtOAc) indicated thepresence of starting material plus 3 other materials. EtOAc and H₂O wereadded to the reaction mixture. The aqueous layer was extracted withEtOAc, and the organic extracts were washed with brine, dried overMgSO₄, and concentrated in vacuo. The crude product was purified bychromatography with gradient elution (100% hexanes to 100% EtOAc)resulting in an off-white solid (90 mg): mp 129° C.; ESIMS m/z 265.0(M+H).

Example 15 Preparation of4-[1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde

Step 1. 4-(1H-[1,2,4]Triazol-3-yl)-benzonitrile. The general procedureoutlined by Lin et al. (J. Org. Chem. 1979, 44, 4163) for preparation of3-(4-nitrophenyl)-1H-[1,2,4]triazole was used. 4-Cyanobenzamide (21.63g, 0.148 mol) was dissolved in DMF-DMA (100 mL) and was stirred atreflux under N₂ for 8 h. The mixture was concentrated to dryness andsuspended in AcOH (50 mL). The vessel was then charged with hydrazinemonohydrate (7.18 mL, 0.148 mmol) and stirred at reflux for 1 h beforeconcentration. The desired 4-(1H-[1,2,4]triazol-3-yl)-benzonitrile wasobtained in 98% purity by trituration with Et₂O followed by filtration(12.17 g, 0.072 mol, 48%).

Step 2.4-[1-(4-Trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]-benzonitrile.The triazole (70 mg, 0.41 mmol), 1-iodo-4-trifluoromethoxybenzene (142mg, 0.493 mmol), Cs₂CO₃ (535 mg, 1.644 mmol), CuI (3 mg, 0.012 mmol),8-hydroxyquinoline (2 mg, 0.012 mmol), and DMF/H₂O (2 mL; 10:1 solution)were combined in a 10 mL CEM Microwave reaction vessel fitted withmagnetic stir bar and subjected to microwave irradiation at 150° C. for30 min. The contents were then filtered and concentrated to drynessaffording the 1,3-diphenyl triazole intermediate (18 mg, 13%).

Step 3.4-[1-(4-Trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde.The nitrile was reduced with DIBAL under conditions previouslydescribed: mp 137-140° C.; ¹H NMR (300 MHz, CDCl₃) δ 10.1 (s, 1H), 8.61(s, 1H), 8.37 (d, J=9 Hz, 2H), 8.0 (d, J=8.4 Hz, 2H), 7.8 (d, J=9 Hz,2H), 7.4 (d, J=8.4 Hz, 2H); ESIMS m/z 334.2 (M+H).

Example 16 Preparation of4-[1-(4-pentafluoroethylsulfanylphenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde

Step 1. 1-Bromo-4-pentafluoroethylsulfanylbenzene. The title compoundwas prepared using perfluoroalkylation conditions originally describedby Popov et. al. J. Fluorine Chem. 1982, 21, 365. To a solution of4-bromobenzenethiol (500 mg, 2.64 mmol, 1.00 eq) and triethylbenzylammonium chloride (60 mg, 0.26 mmol, 0.10 eq) in 10 mL of 1:1 Et₂O/NaOH(25% aq) at 0° C. was bubbled 1,1,1,2,2-pentafluoro-2-iodoethane gas for30 min (>5eq). During this time a UV lamp was directed at the reactionvessel while the temperature was maintained below 10° C. by intermittentuse of an ice bath. The contents were then warmed to room temperature,extracted into Et₂O (300 mL), dried (MgSO₄), and concentrated underreduced pressure. A portion of this crude material was used insubsequent reactions without further purification (200 mg residue: 120mg product, 0.39 mmol, 1.2 eq).

Step 2.4-[1-(4-Pentafluoroethylsulfanylphenyl)-1H-[1,2,4]triazol-3-yl]-benzonitrile.Coupling with 4-(1H-[1,2,4]triazol-3-yl)-benzonitrile as described abovegave4-[1-(4-pentafluoroethylsulfanylphenyl)-1H-[1,2,4]triazol-3-yl]-benzonitrile(70 mg, 46%). Reduction with DIBAL, as described previously, gave thecorresponding aldehyde.

Example 17 Preparation of4-[1-(4-pentafluoroethyloxy-phenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde

Step 1. A solution of 3-p-tolyl-1H-[1,2,4]triazole (4.85 g, 30.5 mmol),4-bromophenyl pentafluoroethyl ether (10.0 g, 34.4 mmol), Cs₂CO₃ (25 g,77 mmol), CuI (1.25 g, 6.5 mmol) and 8-hydroxyquinoline (0.35 g, 2.4mmol) in 9:1 DMF/H₂O (50 mL) was stirred vigorously and heated to 130°C. (internal temperature) for 20 h. The solution was then cooled, pouredinto H₂O, and acidified with 2 N HCl to pH 2. Ether (250 mL) was thenadded and the solution was shaken and filtered before separating layers.The organic layer was dried and concentrated, and the resulting gummysolid was heated with hexanes (100 mL). The hot hexane layer wasdecanted from insoluble residue, the resulting solution cooled to 0° C.and the precipitated solid was filtered and air-dried to furnish1-(4-pentafluoroethyloxy-phenyl)-3-p-tolyl-1H-[1,2,4]triazole (7.0 g,61% based on starting triazole) as an off-white solid: mp 130-132° C.;ESIMS m/z 370.8 (M+H).

Step 2. The product from Step 1 (7.0 g, 18.7 mmol) was dissolved inacetonitrile (200 mL) and stirred at ambient temperature while cericammonium nitrate (32 g, 58 mmol) in H₂O (60 mL) was added in portionsover 10 min. The solution was then heated to reflux for 4 h, cooled, anddiluted with H₂O (200 mL). The solution was extracted with ether (2×200mL), and the combined organic layer was dried and concentrated to givean orange oil. This material was dissolved in dioxane (40 mL) andtreated with a solution of potassium hydroxide (KOH; 5 g, 90 mmol) inH₂O (20 mL). The solution was heated to reflux for 2 h, then cooled anddiluted with H₂O (100 mL). The aldehyde precipitated and was collectedby filtration. Recrystallization from MeOH/H₂O gave the pure aldehyde asa white solid (2.2 g, 30%): mp 137-144° C.; ¹H NMR (300 MHz, CDCl₃) δ10.1 (s, 1H), 8.65 (s, 1H), 8.40 (d, J=8.4 Hz, 2H), 8.0 (d, J=8.4 Hz,2H), 7.85 (d, J=9 Hz, 2H), 7.45 (d, J=9 Hz, 2H); ESIMS m/z 384.2 (M+H).

Example 18 Preparation of4-[1-(4-butylphenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde

Step 1. 4-[1-(4-Butylphenyl)-1H-[1,2,4]triazol-3-yl]-benzonitrile. Asolution of 4-n-butyl phenyl hydrazine (1.0 g, 5 mmol) and4-cyanobenzaldehyde (0.8 g, 6.0 mmol) in i-PrOH (15 mL) was heated on asteam bath for 2 h and then was cooled and diluted with H₂O (5 mL). Theresulting orange solid was filtered and air-dried to give the hydrazone(1.30 g) as a yellow solid, mp 107° C. A solution of this hydrazone (1.1g, 4.0 mmol) and NCS (0.67 g, 5 mmol) in i-PrOH (20 mL) was stirredunder nitrogen at ambient temperature for 2 h, during which time theoriginal solid dissolved and a new solid formed. The resulting orangesolution was then treated with tetrazole (0.45 g, 6.4 mmol) andtriethylamine (960 μL, 7.0 mmol). The orange-brown solution was heatedat reflux for 2 h. The solution was then cooled, diluted with H₂O (25mL), extracted with EtOAc, dried, concentrated, and purified bychromatography (Biotage, 4:1 hexane:EtOAc) to give the triazole (0.42 g,35%) of as an off-white solid: mp 124° C.; ¹H NMR (300 MHz, CDCl₃) δ8.58 (s, 1H), 8.33 (d, J=8 Hz, 2H), 7.78 (d, J=8 Hz, 2H), 7.64 (d, J=8.2Hz, 2H), 7.33 (d, J=8.2 Hz, 2H), 2.70 (t, J=7.8 Hz, 2H), 1.63 (m, 2H),1.38 (m, 2H), 0.95 (t, J=7.5 Hz, 3H); ESIMS m/z 303.1.

Step 2. 4-[1-(4-Butylphenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde.Reduction with DIBAL, as described previously, gave the correspondingaldehyde: mp 124° C.; ¹H NMR (300 MHz, CDCl₃) δ 10.08 (s, 1H), 8.58 (s,1H), 8.37 (d, J=8 Hz, 2H), 7.98 (d, J=8 Hz, 2H), 7.62 (d, J=8.2 Hz, 2H),7.33 (d, J=8.2 Hz, 2H), 2.70 (t, J=7.8 Hz, 2H), 1.63 (m, 2H), 1.38 (m,2H), 0.95 (t, J=7.5 Hz, 3H); ESIMS m/z 306.1.

Example 19 Preparation of4-[1-(4-pentafluoroethylphenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde

Step 1. 1-(4-Pentafluoroethylphenyl)-3-p-tolyl-1H-[1,2,4]triazole.Pentafluoroethyl iodide (521 mg, 2.12 mmol) was condensed into a vialcontaining 1-bromo-4-iodobenzene (300 mg, 1.06 mmol), copper(0) powder(135 mg, 2.12 mmol), and DMSO (5 mL). The vial was then sealed andsubjected to microwave irradiation at 150° C. for 60 min. GC-MS provedconsumption of the starting material yielding both1-bromo-4-pentafluoroethylbenzene and 1-iodo-4-pentafluoroethylbenzeneintermediates. The mixture (1.06 mmol) was transferred to a 250 mL roundbottom flask and 3-p-tolyl-1H-[1,2,4]triazole (169 mg, 1.06 mmol),Cs₂CO₃ (1.38 g, 4.24 mmol), CuI (202 mg, 1.06 mmol), 8-hydroxyquinoline(2 mg, 0.011 mmol), and DMF/H₂O (12 mL; 10:1 solution) were added. Thesolution was stirred at reflux at 160° C. for 6 h. Upon completion, thecooled contents were poured into H₂O and precipitation was allowed for 1h. The precipitate was collected by vacuum filtration and driedovernight in a 45° C. vacuum oven. The crude1-(4-pentafluoroethylphenyl)-3-p-tolyl-1H-[1,2,4]triazole intermediatewas used in step 2 without further purification.

Step 2. Oxidation to the aldehyde. Ammonium cerium(IV) nitrate (3.32 g,4.24 mmol) and the intermediate from Step 1 were combined in a roundbottom flask with acetonitrile and H₂O (20 mL; 1:1). The solution wasstirred at reflux at 110° C. for 4 h, affording a mixture of the3-(4-nitrooxymethyl-phenyl)-1-(4-pentafluoroethyl-phenyl)-1H-[1,2,4]triazoleand4-[1-(4-pentafluoroethyl-phenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehydeintermediates. The acetonitrile was removed under vacuum and the crudeintermediate precipitates were collected by filtration. The material wasthen combined with powdered KOH (178 mg, 3.18 mmol) in dioxane and H₂O(10 mL; 1:1) and was stirred at reflux at 105° C. for 90 min before thedioxane was removed under vacuum allowing precipitation of theintermediate from H₂O. The4-[1-(4-pentafluoroethylphenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehydeintermediate was collected by filtration (35 mg, 0.095 mmol, 9% overallfrom 4-tolyl triazole).

Example 20 Preparation of trifluoromethanesulfonic acid4-[3-(4-formylphenyl)-[1,2,4]triazol-1-yl]-phenyl ester

Step 1. 1-(4-Methoxyphenyl)-3-p-tolyl-1H-[1,2,4]triazole was prepared bycoupling 3-p-tolyl-1H-[1,2,4]triazole with 4-iodoanisole underconditions described in Step 1 of the previous example. This materialwas then demethylated using conditions described in Hitchcock et al.Synlett 2006, 2625. Boron tribromide (1 M solution in hexanes; 1.67 mL,1.67 mmol) was added dropwise to a solution of1-(4-methoxyphenyl)-3-p-tolyl-1H-[1,2,4]triazole (300 mg, 1.28 mmol) inCH₂Cl₂ (10 mL) at 0° C. under N₂. After addition was complete, thevessel was warmed to ambient temperature before refluxing at 40° C. for6 h. The cooled contents were then quenched with H₂O before removal ofthe CH₂Cl₂ and partitioning between EtOAc and H₂O. The organic layer wascollected, washed with brine, dried (MgSO₄), concentrated, and purifiedvia chromatography (3:1:1, hexanes:EtOAc:acetone) to afford the4-(3-p-tolyl-[1,2,4]triazol-1-yl)-phenol intermediate (219 mg, 0.872mmol, 68%). Trifluoromethanesulfonic anhydride (0.16 mL, 0.96 mmol) wasadded dropwise to a solution of the phenol and4-tert-butyl-2,6-dimethylpyridine (142 mg, 0.872 mmol) in CH₂Cl₂ (10 mL)at 0° C. under N₂. The vessel was warmed to ambient temperature beforethe solvent was removed under reduced pressure and the residue purifiedvia chromatography (2:2:1, hexanes:EtOAc:acetone) affording thetrifluoromethanesulfonic acid 4-(3-p-tolyl-[1,2,4]triazol-1-yl)-phenylester intermediate (304 mg, 0.794 mmol, 91%).

Step 2. Oxidation of the 4-methyl intermediate above to thecorresponding aldehyde was carried out using ammonium cerium(IV) nitrateunder conditions described in Step 2 of the previous example.

Example 21 Preparation of4-[5-(4-trifluoromethylphenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde

Terephthalonitrile (115 mg, 0.90 mmol), 4-trifluoromethylbenzoic acidhydrazide (92 mg, 0.450 mmol), K₂CO₃ (31 mg, 0.225 mmol), and n-butylalcohol (˜2 mL) were combined in a 10 mL CEM Microwave reaction vialfitted with magnetic stir bar and subjected to microwave irradiation at150° C. for 30 min. The contents were then filtered and concentrated todryness. Chromatography (3:1 hexanes/EtOAc) afforded the 1,2,4-triazolenitrile (72 mg, 0.230 mmol, 51%). Reduction with DIBAL then generatedthe corresponding aldehyde.

Example 22 Preparation of4-[1-(3,4-dichlorophenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl]-benzaldehyde

Step 1. 4-Cyanophenyl-oxo-acetic acid. A round bottom flask equippedwith mechanical stirrer and reflux condenser was charged withp-cyanoacetophenone (5 g, 34.44 mol), selenium dioxide (SeO₂; 9.55 g,86.1 mmol), and pyridine (˜100 mL). The mixture was stirred at refluxfor 6 h before precipitates were removed by filtration and the filtratewas charged with 10% HCl (aq) (20 mL). The filtrate was extracted intoEtOAc (3×50 mL) and the combined organic layers were further extractedinto nearly saturated NaHCO₃. The aqueous layer was then carefully madeacidic (pH=1) with conc. HCl affording a small crop of the desiredproduct. The remainder of the oxo acetic acid was obtained by extractinginto EtOAc, drying (MgSO₄), and concentration (1.69 g, 28%).

Step 2.4-[1-(3,4-Dichlorophenyl)-5-oxo-4,5-dihydro-1H-[1,2,4]triazol-3-yl]-benzonitrile.A suspension of 4-cyanophenyl-oxo-acetic acid (100 mg, 0.571 mmol),(3,4-dichlorophenyl)hydrazine hydrochloride (122 mg, 0.571 mmol), 12.1 NHCl (5 μL, 0.057 mmol), and H₂O (˜10 mL) in a 25 mL reaction vial wasstirred vigorously at ambient temperature for 24 h. The hydrazone wasobtained by vacuum filtration and placed into a 100 mL round bottomflask with a magnetic stir bar. The flask was then supplemented withtriethylamine (0.08 mL, 0.571 mmol), diphenylphosphoryl azide (157 mg,0.571 mmol), and toluene (20 mL) before heating at 110° C. for 1 h. Uponcooling the contents were quenched with 10% NaOH (aq) and made acidic(pH 1) with conc. HCl. Precipitation was allowed for 15 min before theintermediate was obtained by vacuum filtration and dried overnight in a45° C. vacuum oven (16 mg, 8%). The nitrile was reduced to the aldehydeusing DIBAL under conditions previously described.

Example 23 Preparation of4-[1-(4-Chlorophenyl)-1H-[1,2,3]triazol-4-yl]-benzaldehyde

Following the procedure published by Feldman et al. (Org Lett. 2004, 6,3897), a suspension of 4-ethynylbenzonitrile (50 mg, 0.393 mmol),1-chloro-4-iodobenzene (94 mg, 0.393 mmol), L-proline (9 mg, 0.079mmol), ascorbic acid (7 mg, 0.039 mmol), NaN₃ (31 mg, 0.472 mmol), CuSO₄(3 mg, 0.020 mmol), and Na₂SO₄ (11 mg, 0.079 mmol) in DMSO (1.5 mL) washeated at 65° C. for 24 h. Upon cooling the mixture was diluted with H₂Oand stirred for 30 min at ambient temperature. The intermediate4-[1-(4-chlorophenyl)-1H[1,2,3]triazol-4-yl]-benzonitrile (54 mg, 48%)was then obtained by vacuum filtration after washing with copiousvolumes of H₂O and 20% NH₄OH (˜20 mL). Reduction to the aldehyde wasthen conducted under conditions previously described.

Example 24 Preparation of4-[5-(4-trifluoromethyl-phenyl)-tetrazol-2-yl]-benzaldehyde

This aldehyde was prepared from 4-trifluoromethylbenzaldehyde byfollowing the route described in Roppe et al. J. Med Chem. 2004, 47,4645.

Example 25 Preparation of4-[5-(4-trifluoromethoxyphenyl)-pyridin-3-yl]-benzaldehyde

Step 1. 3,5-Dibromopyridine (4.4 mmol), 4-trifluoromethoxyphenyl boronicacid (5.1 mmol), tetrakis(triphenylphosphine)palladium(0) (0.04 mmol), 2M potassium carbonate (8.44 mmol) and dioxane (21 mL) were combined in avial and heated by microwave for 10 min at 150° C. The reaction mixturewas taken up in ether and washed with brine. The ether layer was driedover magnesium sulfate, was filtered and the solvent removed in vacuo.The crude mixture was purified by silica gel chromatography to yield3-bromo-5-(4-trifluoromethoxyphenyl)-pyridine (130 mg) as a yellowsolid: ¹H NMR (400 MHz, CDCl₃) δ 8.71 (m, 2H), 8.00 (t, J=2.1 Hz, 1H),7.58 (d, J=8.8 Hz, 2H), 7.34 (d, J=8.0 Hz, 2H); EIMS m/z 317 (M⁺).

Step 2. The compound was prepared by palladium-catalyzed arylation ofthe product of step 1 with 4-formylphenyl boronic acid.

Example 26 Preparation of4-[4-(4-trifluoromethoxyphenyl)-pyridin-2-yl]-benzaldehyde

Step 1. The compound was prepared by palladium-catalyzed arylation of2-chloro-4-iodopyridine with 4-trifluoromethoxyphenyl boronic acid.

Step 2. 2-Chloro-4-(4-trifluoromethoxyphenyl)-pyridine (0.55 mmol)starting from 2-chloro-4-iodopyridine, 4-formylphenyl boronic acid (0.82mmol), tetrakis(triphenylphosphine)palladium(0) (0.005 mmol), 2 Mpotassium carbonate (0.55 mL) and dioxane (3 mL) were combined in a vialand irradiated by microwave for 15 min at 150° C. The reaction mixturewas taken up in EtOAc and washed with brine. The organic layer was driedover magnesium sulfate, was filtered and the solvent removed in vacuo.Purification by silica gel chromatography (EtOAc/hexanes) yielded theproduct (120 mg) as an off-white solid: ¹H NMR (400 MHz, CDCl₃) δ 10.11(s, 1H), 8.81 (d, J=4.8 Hz, 1H), 8.24 (d, J=8.7 Hz, 2H), 8.03 (d, J=8.4Hz, 2H), 7.96 (m, 1H), 7.73 (d, J=9.0 Hz, 2H), 7.49 (dd, J=5.3, 1.8 Hz,1H), 7.37 (d, J=8.1 Hz, 2H); EIMS m/z 343 (M⁺).

Example 27 Preparation of4-[6-(4-trifluoromethoxyphenyl)-pyridin-2-yl]-benzaldehyde

Step 1. 4-(6-Bromopyridin-2-yl)-benzaldehyde (0.31 mmol) was prepared asin Puglisi et al. Eur. J. Org. Chem 2003, 8, 1552-1558.

Step 2. 4-[6-(4-Trifluoromethoxyphenyl)-pyridin-2-yl]benzaldehyde.4-(6-Bromo-pyridin-2-yl)-benzaldehyde (0.31 mmol),4-trifluoromethoxyphenyl boronic acid (0.46 mmol),tetrakis(triphenylphosphine)palladium(0) (0.003 mmol), 2 M potassiumcarbonate (0.31 mL) and dioxane (2 mL) were combined in a vial andirradiated by microwave for 10 min at 150° C. The reaction mixture wastaken up in ether and washed with brine. The organic layer was driedover magnesium sulfate, was filtered and the solvent removed in vacuo.Purification by silica gel chromatography (EtOAc/hexanes) yielded theproduct (80 mg) as an off-white solid: mp 109-112° C.; ¹H NMR (400 MHz,CDCl₃) δ 10.11 (s, 1H), 8.32 (d, J=8.5 Hz, 2H), 8.19 (d, J=8.1 Hz, 2H),8.03 (d, J=8.4 Hz, 2H), 7.89 (t, J=7.9 Hz, 1H), 7.79 (d, J=7.7 Hz, 1H),7.74 (d, J=8.0 Hz, 1H), 7.35 (d, J=8.3 Hz, 2H); EIMS m/z 343 (M⁺).

Example 28 Preparation of4-[6-(4-trifluoromethoxyphenyl)-pyrimidin-4-yl]-benzaldehyde

Step 1. 4-Chloro-6-(4-trifluoromethoxyphenyl)-pyrimidine was prepared bypalladium-catalyzed arylation of 4,6-dichloropyrimidine and4-trifluoromethoxyphenyl boronic acid: ¹H NMR (400 MHz, CDCl₃) δ 9.05(s, 1H), 8.14 (d, J=9.8 Hz, 2H), 7.74 (m, 1H), 7.36 (d, J=8.4 Hz, 2H);EIMS m/z 274 (M⁺).

Step 2. The compound was prepared by palladium-catalyzed arylation ofthe product of step 1 with 4-formylphenyl boronic acid: ¹H NMR (400 MHz,CDCl₃) δ 10.15 (s, 1H), 9.38 (d, J=0.9 Hz, 1H), 8.33 (d, J=8.4 Hz, 2H),8.23 (d, J=8.5 Hz, 2H), 8.16 (d, J=0.8 Hz, 1H), 8.08 (d, J=8.8 Hz, 2H),7.40 (d, J=8.1 Hz, 2H); EIMS m/z 344 (M⁺).

Example 29 Preparation of4-[2-(4-trifluoromethoxyphenyl)-pyrimidin-4-yl]-benzaldehyde

Step 1. 4-Chloro-2-(4-trifluoromethoxyphenyl)-pyrimidine. The titlecompound was prepared by palladium-catalyzed arylation of2,4-dichloropyrimidine and 4-trifluoromethoxyphenyl boronic acid: mp70-73° C.; ¹H NMR (400 MHz, CDCl₃) δ 8.68 (d, J=5.6 Hz, 1H), 8.16 (d,J=9.1 Hz, 2H), 7.65 (d, J=5.3 Hz, 1H), 7.36 (dd, J=9.2, 0.9 Hz, 2H);EIMS m/z 274 (M⁺).

Step 2. The compound was prepared by palladium-catalyzed arylation ofthe product of step 1 with 4-formylphenyl boronic acid: ¹H NMR (400 MHz,CDCl₃) δ 10.13 (s, 1H), 8.91 (d, J=4.8 Hz, 1H), 8.74 (d, J=8.5 Hz, 2H),8.28 (d, J=8.4 Hz, 2H), 8.03 (d, J=8.4 Hz, 2H), 7.65 (d, J=5.3 Hz, 1H),7.39 (d, J=8.6 Hz, 2H); EIMS m/z 344 (M⁺).

Example 30 Preparation of4-[4-(4-trifluoromethoxyphenyl)-pyrimidin-2-yl]-benzaldehyde

Step 1. 4-(4-Chloropyrimidin-2-yl)-benzaldehyde. The compound wasprepared by palladium-catalyzed arylation of 2,4-dichloropyrimidine and4-formylphenyl boronic acid: ¹H NMR (400 MHz, CDCl₃) δ 10.13 (s, 1H),8.74 (d, J=5.0 Hz, 1H), 8.27 (d, J=7.8 Hz, 2H), 8.04 (d, J=7.9 Hz, 2H),7.74 (m, 1H); EIMS m/z 218 (M⁺).

Step 2. The compound was prepared by palladium-catalyzed arylation ofthe product of Step 1 with 4-trifluoromethoxyphenyl boronic acid: ¹H NMR(400 MHz, CDCl₃) δ 10.14 (s, 1H), 8.91 (d, J=4.2 Hz, 1H), 8.63 (d, J=8.5Hz, 2H), 8.37 (d, J=8.4 Hz, 2H), 8.06 (d, J=8.8 Hz, 2H), 7.67 (d, J=5.4Hz, 1H), 7.35 (d, J=8.7 Hz, 2H); EIMS m/z 344 (M⁺).

Example 31 Preparation of4-[6-(4-trifluoromethoxyphenyl)-pyrazin-2-yl]-benzaldehyde

Step 1. 2-Chloro-6-(4-trifluoromethoxyphenyl)-pyrazine. The compound wasprepared by palladium-catalyzed arylation of 2,6-dichloropyrazine and4-trifluoromethoxyphenyl boronic acid: mp 58-60° C.; ¹H NMR (400 MHz,CDCl₃) δ 8.94 (s, 1H), 8.57 (s, 1H), 8.10 (d, J=9.0 Hz, 2H), 7.37 (d,J=8.4 Hz, 2H); EIMS m/z 274 (M⁺).

Step 2. The compound was prepared by palladium-catalyzed arylation ofthe product of step 1 with 4-formylphenyl boronic acid: ¹H NMR (400 MHz,CDCl₃) δ 10.13 (s, 1H), 9.07 (s, 1H), 9.03 (s, 1H), 8.33 (d, J=8.1 Hz,2H), 8.21 (d, J=8.7 Hz, 2H), 8.07 (d, J=7.6 Hz, 2H), 7.40 (d, J=8.3 Hz,2H); EIMS m/z 344 (M⁺).

Example 32 Preparation of4-[2-(4-trifluoromethoxyphenyl)-pyrimidin-5-yl]-benzaldehyde

Step 1. 4-(2-Chloropyrimidin-5-yl)-benzaldehyde. The compound wasprepared by palladium-catalyzed arylation of 2,5-dichloropyrimidine and4-formylphenyl boronic acid.

Step 2. 4-(2-Chloropyrimidin-5-yl)-benzaldehyde (0.92 mmol),4-trifluoromethoxyphenyl boronic acid (1.10 mmol),dichlorobis(triphenylphosphine)-palladium(II) (0.01 mmol), 2 M potassiumcarbonate (0.92 mL) and dioxane (5 mL) were combined in a vial andirradiated by microwave for 10 min at 150° C. The organic layer from thereaction mixture was loaded directly onto silica and dried in vacuo.Purification by silica gel chromatography (EtOAc/hexanes) yielded theproduct (140 mg) as a white solid: ¹H NMR (400 MHz, CDCl₃) δ 10.11 (s,1H), 9.07 (s, 2H), 8.57 (d, J=9.0 Hz, 2H), 8.07 (d, J=8.5 Hz, 2H), 7.82(d, J=8.3 Hz, 2H), 7.35 (d, J=8.3 Hz, 2H); EIMS m/z 344 (M⁺).

Example 33 Preparation of4-[5-(4-trifluoromethoxyphenyl)-pyrimidin-2-yl]-benzaldehyde

Step 1. 2-Chloro-5-(4-trifluoromethoxyphenyl)-pyrimidine. The compoundwas prepared by palladium-catalyzed arylation of 2,5-dichloropyrimidinewith 4-trifluoromethoxyphenyl boronic acid.

Step 2. 2-Chloro-5-(4-trifluoromethoxyphenyl)-pyrimidine (4.22 mmol),4-formylphenyl boronic acid (5.1 mmol),dichlorobis(triphenylphosphine)palladium(II) (0.05 mmol), 2 M potassiumcarbonate (4.2 mL) and dioxane (21 mL) were combined in a vial andirradiated by microwave for 20 min at 150° C. The organic layer from thereaction mixture was loaded directly onto silica and dried in vacuo.Purification by silica gel chromatography (EtOAc/hexanes) yielded theproduct (75 mg) as a white solid: ¹H NMR (400 MHz, CDCl₃) δ 10.13 (s,1H), 9.06 (s, 2H), 8.68 (d, J=8.8 Hz, 2H), 8.03 (d, J=8.3 Hz, 2H), 7.68(d, J=8.8 Hz, 2H), 7.40 (d, J=8.7 Hz, 2H); EIMS m/z 344 (M⁺).

Example 34 Preparation of(E)-N-(4-dimethylamino)phenyl)-2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4triazol-3-yl)benzylidene)hydrazine-carbothioamide(Compound 1) [Synthesis Method A]

Step 1.(E)-3-(4-(Hydrazonomethyl)phenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole.To a 250 mL round-bottomed flask containing hydrazine hydrate (64% aqsolution; 7.27 mL, 15.0 mmol) in EtOH (100 mL) at 80° C. was added4-[1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde(5.00 g, 1.50 mmol) portionwise over 5 min. The solution was stirred atreflux for an additional 3 h before being diluted with H₂O (300 mL) andcooled to 0° C. The precipitated product was collected by vacuumfiltration as a white solid (4.89 g, 93%) mp 222-226° C.; ¹H NMR (400MHz, DMSO-d₆) δ 8.59 (s, 1H), 8.22 (d, J=8.2 Hz, 2H), 7.84-7.79 (m, 2H),7.66 (d, J=8.3 Hz, 2H), 7.41 (d, J=8.2 Hz, 2H), 7.29 (s, 1H), 5.63 (brs, 2H); ESIMS m/z 348 (M+H).

Step 2. To a 25 mL round-bottomed flask containing(E)-3-(4-(hydrazonomethyl)phenyl)-1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazole(250 mg, 0.720 mmol) in THF (10 mL) was added4-isothiocyanato-N,N-dimethylaniline (385 mg, 2.16 mmol). The contentswere heated at 65° C. with stirring for 2 h before the solvent wasremoved under reduced pressure. The residue was slurried in CH₂Cl₂ (10mL) resulting in precipitation of product material. The desired productwas obtained as a yellow solid via vacuum filtration (350 mg, 93%): mp205-208° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 11.78 (s, 1H), 10.02 (s, 1H),9.42 (s, 1H), 8.19-7.99 (m, 6H), 7.64 (d, J=8.3 Hz, 2H), 7.28 (d, J=8.3Hz, 2H), 7.73 (d, J=8.3 Hz, 2H), 2.92 (s, 6H); ESIMS m/z 526 (M+H).

Example 35 Preparation ofN-(3-(dimethylamino)phenyl)-2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide (Compound 2) [Synthesis Method B]

Step 1. (E)-Methyl2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazinecarbodithioate.To a 250 mL round-bottom flask containing hydrazinecarbodithioic acidmethyl ester (2.38 g, 1.95 mmol) in EtOH (100 mL) was added4-[1-(4-trifluoromethoxyphenyl)-1H-[1,2,4]triazol-3-yl]-benzaldehyde(5.00 g, 1.50 mmol). The vessel was heated at 80° C. for 3 h beforebeing diluted with H₂O (300 mL) and cooled to 0° C. The precipitatedproduct was collected by vacuum filtration as an off-white solid (6.13g, 93%) mp 204-206° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 13.39 (s, 1H), 9.43(s, 1H), 8.38 (s, 1H), 8.21 (d, J=8.3 Hz, 2H), 8.09 (d, J=8.4 Hz, 2H),7.88 (d, J=8.4 Hz, 2H), 7.62 (d, J=8.3 Hz, 2H), 2.57 (s, 3H); ESIMS m/z438 (M+H).

Step 2. To a 50 mL round-bottomed flask containing (E)-methyl2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazinecarbodithioate(250 mg, 0.571 mmol) in DMF (3 mL) was addedN1,N1-dimethylbenzene-1,3-diamine (195 mg, 1.43 mmol). The contents wereheated at 150° C. with stirring for 5 h before the solution was allowedto cool overnight. The mixture was filtered, and the filtrate purifiedvia RP-HPLC to afford the desired material (235 mg, 78%) as an off-whitesolid: mp 192-194° C.; ¹H NMR (400 MHz, DMSO-d₆) δ 11.82 (s, 1H), 10.04(s, 1H), 9.41 (s, 1H), 8.19 (s, 1H), 8.16-7.99 (m, 6H), 7.61 (d, J=8.3Hz, 2H), 7.16 (t, J=7.2 Hz, 1H), 7.01 (m, 1H), 6.87 (m, 1H), 6.58 (m,1H), 2.88 (s, 6H); ESIMS m/z 526 ([M+H]⁺).

Example 36 Preparation ofN-benzyl-2-(4-(1-(4-(trifluoromethoxy)phenyl)-1H-1,2,4-triazol-3-yl)benzylidene)hydrazinecarbothioamide(Compound 3) [Synthesis Method C]

To a 50 mL round-bottomed flask containing4-[1-[4-(trifluoromethoxy)phenyl]-1,2,4-triazol-3-yl]benzaldehyde (500mg, 1.5 mmol) in EtOH (3 mL) was added 4-benzylthiosemicarbazide (650mg, 3.6 mmol). The reaction mixture was heated at 80° C. overnight. H₂Owas added upon completion of the reaction and the crude product materialwas isolated by vacuum filtration. The title compound was isolated viaRP-HPLC as a white solid (390 mg, 52% yield): mp 220-224° C.; ¹H NMR(400 MHz, CDCl₃) δ 9.29 (s, 1H), 8.59 (s, 1H), 8.21 (d, J=8.4 Hz, 2H),7.85-7.79 (m, 3H), 7.71 (d, J=8.4 Hz, 2H), 7.46-7.30 (m, 8H), 5.01 (d,J=5.8 Hz, 2H); ESIMS 497.2 (M+H).

Compounds 4-159 in Table 1 were synthesized in accordance with theexamples above.

The compounds were tested against beet armyworm and corn earworm usingprocedures described in the following examples and reported in Table 2.

In each case of Table 2, the rating scale is as follows:

% Control (or Mortality) Rating 50-100 A Less than 50 B Not tested C

Example 37 Insecticidal Test for Beet Armyworm (Spodoptera exigua)

Bioassays on beet armyworm (BAW; Spodoptera exigua: Lepidoptera) wereconducted using a 128-well diet tray assay. Three to five second instarBAW larvae were placed in each well (3 mL) of the diet tray that hadbeen previously filled with 1 mL of artificial diet to which 50 μg/cm²of the test compound (dissolved in 50 μL of 90:10 acetone-water mixture)had been applied (to each of eight wells) and then allowed to dry. Trayswere covered with a clear self-adhesive cover, and held at 25° C., 14:10light-dark for six days. Percent mortality was recorded for the larvaein each well; activity in the eight wells was then averaged. The resultsfor both bioassays are indicated in Table 2.

Example 38 Insecticidal Test for Corn Earworm (Helicoverpa zea)

Bioassays on corn earworm (CEW; Helicoverpa zea: Lepidoptera) wereconducted using a 128-well diet tray assay. Three to five second instarCEW larvae were placed in each well (3 mL) of the diet tray that hadbeen previously filled with 1 mL of artificial diet to which 50 μg/cm²of the test compound (dissolved in 50 μL of 90:10 acetone-water mixture)had been applied (to each of eight wells) and then allowed to dry. Trayswere covered with a clear self-adhesive cover, and held at 25° C., 14:10light-dark for six days. Percent mortality was recorded for the larvaein each well; activity in the eight wells was then averaged. The resultsfor both bioassays are indicated in Table 2.

The compounds were also tested against green peach aphid using aprocedure described in the following example and reported in Table 2.

In each case of Table 2, the rating scale is as follows:

% Control (or Mortality) Rating 80-100 A Less than 80 B Not tested C

Example 39 Insecticidal Test for Green Peach Aphid (Myzus persicae) inFoliar Spray Assay

Cabbage seedlings grown in 3-inch pots, with 2-3 small (3-5 cm) trueleaves, were used as test substrate. The seedlings were infested with20-50 green peach aphids (wingless adult and nymph) one day prior tochemical application. Four pots with individual seedlings were used foreach treatment. Compounds (2 mg) were dissolved in 2 mL ofacetone/methanol (1:1) solvent, forming stock solutions of 1000 ppm. Thestock solutions were diluted 5× with 0.025% Tween 20 in H₂O to obtainthe test solution at 200 ppm. A hand-held Devilbiss sprayer was used forspraying a solution to both sides of cabbage leaves until runoff.Reference plants (solvent check) were sprayed with the diluent only.Treated plants were held in a holding room for three days atapproximately 25° C. and 40% relative humidity (RH) prior to grading.Evaluation was conducted by counting the number of live aphids per plantunder a microscope. Insecticidal activity data, measured by usingAbbott's correction formula, are presented in Table 2:

Corrected % Control=100*(X−Y)/X

-   -   where X=No. of live aphids on solvent check plants        -   Y=No. of live aphids on treated plants

Acid and Salt Derivatives and Solvates

The compounds disclosed in this invention can be in the form ofpesticidally acceptable acid addition salts.

By way of non-limiting example, an amine function can form salts withhydrochloric, hydrobromic, sulfuric, phosphoric, acetic, benzoic,citric, malonic, salicylic, malic, fumaric, oxalic, succinic, tartaric,lactic, gluconic, ascorbic, maleic, aspartic, benzenesulfonic,methanesulfonic, ethanesulfonic, hydroxymethanesulfonic, andhydroxyethanesulfonic acids.

Additionally, by way of non-limiting example, an acid function can formsalts including those derived from alkali or alkaline earth metals andthose derived from ammonia and amines. Examples of preferred cationsinclude sodium, potassium, magnesium, and aminium cations.

The salts are prepared by contacting the free base form with asufficient amount of the desired acid to produce a salt. The free baseforms may be regenerated by treating the salt with a suitable diluteaqueous base solution such as dilute aqueous NaOH, potassium carbonate,ammonia, and sodium bicarbonate. As an example, in many cases, apesticide is modified to a more water soluble form e.g.2,4-dichlorophenoxy acetic acid dimethyl amine salt is a more watersoluble form of 2,4-dichlorophenoxy acetic acid a well known herbicide.

The compounds disclosed in this invention can also form stable complexeswith solvent molecules that remain intact after the non-complexedsolvent molecules are removed from the compounds. These complexes areoften referred to as “solvates.”

Stereoisomers

Certain compounds disclosed in this document can exist as one or morestereoisomers. The various stereoisomers include geometric isomers,diastereomers, and enantiomers. Thus, the compounds disclosed in thisinvention include racemic mixtures, individual stereoisomers, andoptically active mixtures. It will be appreciated by those skilled inthe art that one stereoisomer may be more active than the others.Individual stereoisomers and optically active mixtures may be obtainedby selective synthetic procedures, by conventional synthetic proceduresusing resolved starting materials, or by conventional resolutionprocedures.

Pests

In another embodiment, the invention disclosed in this document can beused to control pests.

In another embodiment, the invention disclosed in this document can beused to control pests of the Phylum Nematoda.

In another embodiment, the invention disclosed in this document can beused to control pests of the Phylum Arthropoda.

In another embodiment, the invention disclosed in this document can beused to control pests of the Subphylum Chelicerata.

In another embodiment, the invention disclosed in this document can beused to control pests of the Class Arachnida.

In another embodiment, the invention disclosed in this document can beused to control pests of the Subphylum Myriapoda.

In another embodiment, the invention disclosed in this document can beused to control pests of the Class Symphyla.

In another embodiment, the invention disclosed in this document can beused to control pests of the Subphylum Hexapoda.

In another embodiment, the invention disclosed in this document can beused to control pests of the Class Insecta.

In another embodiment, the invention disclosed in this document can beused to control Coleoptera (beetles). A non-exhaustive list of thesepests includes, but is not limited to, Acanthoscelides spp. (weevils),Acanthoscelides obtectus (common bean weevil), Agrilus planipennis(emerald ash borer), Agriotes spp. (wireworms), Anoplophora glabripennis(Asian longhorned beetle), Anthonomus spp. (weevils), Anthonomus grandis(boll weevil), Aphidius spp., Apion spp. (weevils), Apogonia spp.(grubs), Ataenius spretulus (Black Turgrass Ataenius), Atomaria linearis(pygmy mangold beetle), Aulacophore spp., Bothynoderes punctiventris(beet root weevil), Bruchus spp. (weevils), Bruchus pisorum (peaweevil), Cacoesia spp., Callosobruchus maculatus (southern cow peaweevil), Carpophilus hemipteras (dried fruit beetle), Cassida vittata,Cerosterna spp., Cerotoma spp. (chrysomeids), Cerotoma trifurcata (beanleaf beetle), Ceutorhynchus spp. (weevils), Ceutorhynchus assimilis(cabbage seedpod weevil), Ceutorhynchus napi (cabbage curculio),Chaetocnema spp. (chrysomelids), Colaspis spp. (soil beetles), Conoderusscalaris, Conoderus stigmosus, Conotrachelus nenuphar (plum curculio),Cotinus nitidis (Green June beetle), Crioceris asparagi (asparagusbeetle), Cryptolestes ferrugineus (rusty grain beetle), Cryptolestespusillus (flat grain beetle), Cryptolestes turcicus (Turkish grainbeetle), Ctenicera spp. (wireworms), Curculio spp. (weevils),Cyclocephala spp. (grubs), Cylindrocpturus adspersus (sunflower stemweevil), Deporaus marginatus (mango leaf-cutting weevil), Dermesteslardarius (larder beetle), Dermestes maculates (hide beetle), Diabroticaspp. (chrysolemids), Epilachna varivestis (Mexican bean beetle),Faustinus cubae, Hylobius pales (pales weevil), Hypera spp. (weevils),Hypera postica (alfalfa weevil), Hyperdoes spp. (Hyperodes weevil),Hypothenemus hampei (coffee berry beetle), Ips spp. (engravers),Lasioderma serricorne (cigarette beetle), Leptinotarsa decemlineata(Colorado potato beetle), Liogenys fuscus, Liogenys suturalis,Lissorhoptrus oryzophilus (rice water weevil), Lyctus spp. (woodbeetles/powder post beetles), Maecolaspis joliveti, Megascelis spp.,Melanotus communis, Meligethes spp., Meligethes aeneus (blossom beetle),Melolontha melolontha (common European cockchafer), Oberea brevis,Oberea linearis, Oryctes rhinoceros (date palm beetle), Oryzaephilusmercator (merchant grain beetle), Oryzaephilus surinamensis (sawtoothedgrain beetle), Otiorhynchus spp. (weevils), Oulema melanopus (cerealleaf beetle), Oulema oryzae, Pantomorus spp. (weevils), Phyllophaga spp.(May/June beetle), Phyllophaga cuyabana, Phyllotreta spp.(chrysomelids), Phynchites spp., Popillia japonica (Japanese beetle),Prostephanus truncates (larger grain borer), Rhizopertha dominica(lesser grain borer), Rhizotrogus spp. (European chafer), Rhynchophorusspp. (weevils), Scolytus spp. (wood beetles), Shenophorus spp.(Billbug), Sitona lineatus (pea leaf weevil), Sitophilus spp. (grainweevils), Sitophilus granaries (granary weevil), Sitophilus oryzae (riceweevil), Stegobium paniceum (drugstore beetle), Tribolium spp. (flourbeetles), Tribolium castaneum (red flour beetle), Tribolium confusum(confused flour beetle), Trogoderma variabile (warehouse beetle), andZabrus tenebioides.

In another embodiment, the invention disclosed in this document can beused to control Dermaptera (earwigs).

In another embodiment, the invention disclosed in this document can beused to control Dictyoptera (cockroaches). A non-exhaustive list ofthese pests includes, but is not limited to, Blattella germanica (Germancockroach), Blatta orientalis (oriental cockroach), Parcoblattapennylvanica, Periplaneta americana (American cockroach), Periplanetaaustraloasiae (Australian cockroach), Periplaneta brunnea (browncockroach), Periplaneta fuliginosa (smokybrown cockroach), Pyncoselussuninamensis (Surinam cockroach), and Supella longipalpa (brownbandedcockroach).

In another embodiment, the invention disclosed in this document can beused to control Diptera (true flies). A non-exhaustive list of thesepests includes, but is not limited to, Aedes spp. (mosquitoes), Agromyzafrontella (alfalfa blotch leafminer), Agromyza spp. (leaf miner flies),Anastrepha spp. (fruit flies), Anastrepha suspensa (Caribbean fruitfly), Anopheles spp. (mosquitoes), Batrocera spp. (fruit flies),Bactrocera cucurbitae (melon fly), Bactrocera dorsalis (oriental fruitfly), Ceratitis spp. (fruit flies), Ceratitis capitata (Mediterraneanfruit fly), Chrysops spp. (deer flies), Cochliomyia spp. (screwworms),Contarinia spp. (gall midges), Culex spp. (mosquitoes), Dasineura spp.(gall midges), Dasineura brassicae (cabbage gall midge), Delia spp.,Delia platura (seedcorn maggot), Drosophila spp. (vinegar flies), Fanniaspp. (filth flies), Fannia canicularis (little house fly), Fanniascalaris (latrine fly), Gasterophilus intestinalis (horse bot fly),Gracillia perseae, Haematobia irritans (horn fly), Hylemyia spp. (rootmaggots), Hypoderma lineatum (common cattle grub), Liriomyza spp.(leafminer flies), Liriomyza brassica (serpentine leafminer), Melophagusovinus (sheep ked), Musca spp. (muscid flies), Musca autumnalis (facefly), Musca domestica (house fly), Oestrus ovis (sheep bot fly),Oscinella frit (frit fly), Pegomyia betae (beet leafminer), Phorbiaspp., Psila rosae (carrot rust fly), Rhagoletis cerasi (cherry fruitfly), Rhagoletis pomonella (apple maggot), Sitodiplosis mosellana(orange wheat blossom midge), Stomoxys calcitrans (stable fly), Tabanusspp. (horse flies), and Tipula spp. (crane flies).

In another embodiment, the invention disclosed in this document can beused to control Hemiptera (true bugs). A non-exhaustive list of thesepests includes, but is not limited to, Acrosternum hilare (green stinkbug), Blissus leucopterus (chinch bug), Calocoris norvegicus (potatomirid), Cimex hemipterus (tropical bed bug), Cimex lectularius (bedbug), Dagbertus fasciatus, Dichelops furcatus, Dysdercus suturellus(cotton stainer), Edessa meditabunda, Eurygaster maura (cereal bug),Euschistus heros, Euschistus servus (brown stink bug), Helopeltisantonii, Helopeltis theivora (tea blight plantbug), Lagynotomus spp.(stink bugs), Leptocorisa oratorius, Leptocorisa varicornis, Lygus spp.(plant bugs), Lygus hesperus (western tarnished plant bug),Maconellicoccus hirsutus, Neurocolpus longirostris, Nezara viridula(southern green stink bug), Phytocoris spp. (plant bugs), Phytocoriscalifornicus, Phytocoris relativus, Piezodorus guildingi, Poecilocapsuslineatus (fourlined plant bug), Psallus vaccinicola, Pseudacystaperseae, Scaptocoris castanea, and Triatoma spp. (bloodsucking conenosebugs/kissing bugs).

In another embodiment, the invention disclosed in this document can beused to control Homoptera (aphids, scales, whiteflies, leafhoppers). Anon-exhaustive list of these pests includes, but is not limited to,Acrythosiphon pisum (pea aphid), Adelges spp. (adelgids), Aleurodesproletella (cabbage whitefly), Aleurodicus disperses, Aleurothrixusfloccosus (woolly whitefly), Aluacaspis spp., Amrasca bigutellabigutella, Aphrophora spp. (leafhoppers), Aonidiella aurantii(California red scale), Aphis spp. (aphids), Aphis gossypii (cottonaphid), Aphis pomi (apple aphid), Aulacorthum solani (foxglove aphid),Bemisia spp. (whiteflies), Bemisia argentifolii, Bemisia tabaci(sweetpotato whitefly), Brachycolus noxius (Russian aphid),Brachycorynella asparagi (asparagus aphid), Brevennia rehi, Brevicorynebrassicae (cabbage aphid), Ceroplastes spp. (scales), Ceroplastes rubens(red wax scale), Chionaspis spp. (scales), Chrysomphalus spp. (scales),Coccus spp. (scales), Dysaphis plantaginea (rosy apple aphid), Empoascaspp. (leafhoppers), Eriosoma lanigerum (woolly apple aphid), Iceryapurchasi (cottony cushion scale), Idioscopus nitidulus (mangoleafhopper), Laodelphax striatellus (smaller brown planthopper),Lepidosaphes spp., Macrosiphum spp., Macrosiphum euphorbiae (potatoaphid), Macrosiphum granarium (English grain aphid), Macrosiphum rosae(rose aphid), Macrosteles quadrilineatus (aster leafhopper), Mahanarvafrimbiolata, Metopolophium dirhodum (rose grain aphid), Mictislongicornis, Myzus persicae (green peach aphid), Nephotettix spp.(leafhoppers), Nephotettix cinctipes (green leafhopper), Nilaparvatalugens (brown planthopper), Parlatoria pergandii (chaff scale),Parlatoria ziziphi (ebony scale), Peregrinus maidis (corn delphacid),Philaenus spp. (spittlebugs), Phylloxera vitifoliae (grape phylloxera),Physokermes piceae (spruce bud scale), Planococcus spp. (mealybugs),Pseudococcus spp. (mealybugs), Pseudococcus brevipes (pine applemealybug), Quadraspidiotus perniciosus (San Jose scale), Rhapalosiphumspp. (aphids), Rhapalosiphum maida (corn leaf aphid), Rhapalosiphum padi(oat bird-cherry aphid), Saissetia spp. (scales), Saissetia oleae (blackscale), Schizaphis graminum (greenbug), Sitobion avenae (English grainaphid), Sogatella furcifera (white-backed planthopper), Therioaphis spp.(aphids), Toumeyella spp. (scales), Toxoptera spp. (aphids),Trialeurodes spp. (whiteflies), Trialeurodes vaporariorum (greenhousewhitefly), Trialeurodes abutiloneus (bandedwing whitefly), Unaspis spp.(scales), Unaspis yanonensis (arrowhead scale), and Zulia entreriana.

In another embodiment, the invention disclosed in this document can beused to control Hymenoptera (ants, wasps, and bees). A non-exhaustivelist of these pests includes, but is not limited to, Acromyrrmex spp.,Athalia rosae, Atta spp. (leafcutting ants), Camponotus spp. (carpenterants), Diprion spp. (sawflies), Formica spp. (ants), Iridomyrmex humilis(Argentine ant), Monomorium ssp., Monomorium minumum (little black ant),Monomorium pharaonis (Pharaoh ant), Neodiprion spp. (sawflies),Pogonomyrmex spp. (harvester ants), Polistes spp. (paper wasps),Solenopsis spp. (fire ants), Tapoinoma sessile (odorous house ant),Tetranomorium spp. (pavement ants), Vespula spp. (yellow jackets), andXylocopa spp. (carpenter bees).

In another embodiment, the invention disclosed in this document can beused to control Isoptera (termites). A non-exhaustive list of thesepests includes, but is not limited to, Coptotermes spp., Coptotermescurvignathus, Coptotermes frenchii, Coptotermes formosanus (Formosansubterranean termite), Cornitermes spp. (nasute termites), Cryptotermesspp. (drywood termites), Heterotermes spp. (desert subterraneantermites), Heterotermes aureus, Kalotermes spp. (drywood termites),Incistitermes spp. (drywood termites), Macrotermes spp. (fungus growingtermites), Marginitermes spp. (drywood termites), Microcerotermes spp.(harvester termites), Microtermes obesi, Procornitermes spp.,Reticulitermes spp. (subterranean termites), Reticulitermes banyulensis,Reticulitermes grassei, Reticulitermes flavipes (eastern subterraneantermite), Reticulitermes hageni, Reticulitermes hesperus (westernsubterranean termite), Reticulitermes santonensis, Reticulitermessperatus, Reticulitermes tibialis, Reticulitermes virginicus,Schedorhinotermes spp., and Zootermopsis spp. (rotten-wood termites).

In another embodiment, the invention disclosed in this document can beused to control Lepidoptera (moths and butterflies). A non-exhaustivelist of these pests includes, but is not limited to, Achoea janata,Adoxophyes spp., Adoxophyes orana, Agrotis spp. (cutworms), Agrotisipsilon (black cutworm), Alabama argillacea (cotton leafworm), Amorbiacuneana, Amyelosis transitella (navel orangeworm), Anacamptodesdefectaria, Anarsia lineatella (peach twig borer), Anomis sabulifera(jute looper), Anticarsia gemmatalis (velvetbean caterpillar), Archipsargyrospila (fruit tree leafroller), Archips rosana (rose leaf roller),Argyrotaenia spp. (tortricid moths), Argyrotaenia citrana (orangetortrix), Autographa gamma, Bonagota cranaodes, Borbo cinnara (rice leaffolder), Bucculatrix thurberiella (cotton leaf perforator), Caloptiliaspp. (leaf miners), Capua reticulana, Carposina niponensis (peach fruitmoth), Chilo spp., Chlumetia transversa (mango shoot borer),Choristoneura rosaceana (oblique banded leaf roller), Chrysodeixis spp.,Cnaphalocerus medinalis (grass leafroller), Colias spp., Conpomorphacramerella, Cossus cossus (carpenter moth), Crambus spp. (Sod webworms),Cydia funebrana (plum fruit moth), Cydia molesta (oriental fruit moth),Cydia nignicana (pea moth), Cydia pomonella (codling moth), Darnadiducta, Diaphania spp. (stem borers), Diatraea spp. (stalk borers),Diatraea saccharalis (sugarcane borer), Diatraea graniosella(southwestern corn borer), Earias spp. (bollworms), Earias insulata(Egyptian bollworm), Earias vitella (rough northern bollworm),Ecdytopopha aurantianum, Elasmopalpus lignosellus (lesser cornstalkborer), Epiphysias postruttana (light brown apple moth), Ephestia spp.(flour moths), Ephestia cautella (almond moth), Ephestia elutella(tobacco moth), Ephestia kuehniella (Mediterranean flour moth), Epimecesspp., Epinotia aporema, Erionota thrax (banana skipper), Eupoeciliaambiguella (grape berry moth), Euxoa auxiliaris (army cutworm), Feltiaspp. (cutworms), Gortyna spp. (stemborers), Grapholita molesta (orientalfruit moth), Hedylepta indicata (bean leaf webber), Helicoverpa spp.(noctuid moths), Helicoverpa armigera (cotton bollworm), Helicoverpa zea(bollworm/corn earworm), Heliothis spp. (noctuid moths), Heliothisvirescens (tobacco budworm), Hellula undalis (cabbage webworm),Indarbela spp. (root borers), Keiferia lycopersicella (tomato pinworm),Leucinodes orbonalis (eggplant fruit borer), Leucoptera malifoliella,Lithocollectis spp., Lobesia botrana (grape fruit moth), Loxagrotis spp.(noctuid moths), Loxagrotis albicosta (western bean cutworm), Lymantriadispar (gypsy moth), Lyonetia clerkella (apple leaf miner), Mahasenacorbetti (oil palm bagworm), Malacosoma spp. (tent caterpillars),Mamestra brassicae (cabbage armyworm), Maruca testulalis (bean podborer), Metisa plana (bagworm), Mythimna unipuncta (true armyworm),Neoleucinodes elegantalis (small tomato borer), Nymphula depunctalis(rice caseworm), Operophthera brumata (winter moth), Ostrinia nubilalis(European corn borer), Oxydia vesulia, Pandemis cerasana (common curranttortrix), Pandemis heparana (brown apple tortrix), Papilio demodocus,Pectinophora gossypiella (pink bollworm), Peridroma spp. (cutworms),Peridroma saucia (variegated cutworm), Perileucoptera coffeella (whitecoffee leafminer), Phthorimaea operculella (potato tuber moth),Phyllocnisitis citrella, Phyllonorycter spp. (leafminers), Pieris rapae(imported cabbageworm), Plathypena scabs, Plodia interpunctella (Indianmeal moth), Plutella xylostella (diamondback moth), Polychrosis viteana(grape berry moth), Prays endocarps, Prays oleae (olive moth),Pseudaletia spp. (noctuid moths), Pseudaletia unipunctata (armyworm),Pseudoplusia includens (soybean looper), Rachiplusia nu, Scirpophagaincertulas, Sesamia spp. (stemborers), Sesamia inferens (pink rice stemborer), Sesamia nonagrioides, Setora nitens, Sitotroga cerealella(Angoumois grain moth), Sparganothis pilleriana, Spodoptera spp.(armyworms), Spodoptera exigua (beet armyworm), Spodoptera frugiperda(fall armyworm), Spodoptera oridania (southern armyworm), Synanthedonspp. (root borers), Thecla basilides, Thermisia gemmatalis, Tineolabisselliella (webbing clothes moth), Trichoplusia ni (cabbage looper),Tuta absoluta, Yponomeuta spp., Zeuzera coffeae (red branch borer), andZeuzera pyrina (leopard moth).

In another embodiment, the invention disclosed in this document can beused to control Mallophaga (chewing lice). A non-exhaustive list ofthese pests includes, but is not limited to, Bovicola ovis (sheep bitinglouse), Menacanthus stramineus (chicken body louse), and Menopongallinea (common hen louse).

In another embodiment, the invention disclosed in this document can beused to control Orthoptera (grasshoppers, locusts, and crickets). Anon-exhaustive list of these pests includes, but is not limited to,Anabrus simplex (Mormon cricket), Gryllotalpidae (mole crickets),Locusta migratoria, Melanoplus spp. (grasshoppers), Microcentrumretinerve (angular winged katydid), Pterophylla spp. (katydids),chistocerca gregaria, Scudderia furcata (fork tailed bush katydid), andValanga nigricorni.

In another embodiment, the invention disclosed in this document can beused to control Phthiraptera (sucking lice). A non-exhaustive list ofthese pests includes, but is not limited to, Haematopinus spp. (cattleand hog lice), Linognathus ovillus (sheep louse), Pediculus humanuscapitis (human body louse), Pediculus humanus humanus (human body lice),and Pthirus pubis (crab louse),

In another embodiment, the invention disclosed in this document can beused to control Siphonaptera (fleas). A non-exhaustive list of thesepests includes, but is not limited to, Ctenocephalides canis (dog flea),Ctenocephalides felis (cat flea), and Pulex irritans (human flea).

In another embodiment, the invention disclosed in this document can beused to control Thysanoptera (thrips). A non-exhaustive list of thesepests includes, but is not limited to, Frankliniella fusca (tobaccothrips), Frankliniella occidentalis (western flower thrips),Frankliniella shultzei Frankliniella williamsi (corn thrips),Heliothrips haemorrhaidalis (greenhouse thrips), Riphiphorothripscruentatus, Scirtothrips spp., Scirtothrips citri (citrus thrips),Scirtothrips dorsalis (yellow tea thrips), Taeniothripsrhopalantennalis, and Thrips spp.

In another embodiment, the invention disclosed in this document can beused to control Thysanura (bristletails). A non-exhaustive list of thesepests includes, but is not limited to, Lepisma spp. (silverfish) andThermobia spp. (firebrats).

In another embodiment, the invention disclosed in this document can beused to control Acarina (mites and ticks). A non-exhaustive list ofthese pests includes, but is not limited to, Acarapsis woodi (trachealmite of honeybees), Acarus spp. (food mites), Acarus siro (grain mite),Aceria mangiferae (mango bud mite), Aculops spp., Aculops lycopersici(tomato russet mite), Aculops pelekasi, Aculus pelekassi, Aculusschlechtendali (apple rust mite), Amblyomma americanum (lone star tick),Boophilus spp. (ticks), Brevipalpus obovatus (privet mite), Brevipalpusphoenicis (red and black flat mite), Demodex spp. (mange mites),Dermacentor spp. (hard ticks), Dermacentor variabilis (American dogtick), Dermatophagoides pteronyssinus (house dust mite), Eotetranycusspp., Eotetranychus carpini (yellow spider mite), Epitimerus spp.,Eriophyes spp., Ixodes spp. (ticks), Metatetranycus spp., Notoedrescati, Oligonychus spp., Oligonychus coffee, Oligonychus ilicus (southernred mite), Panonychus spp., Panonychus citri (citrus red mite),Panonychus ulmi (European red mite), Phyllocoptruta oleivora (citrusrust mite), Polyphagotarsonemun latus (broad mite), Rhipicephalussanguineus (brown dog tick), Rhizoglyphus spp. (bulb mites), Sarcoptesscabiei (itch mite), Tegolophus perseaflorae, Tetranychus spp.,Tetranychus urticae (two-spotted spider mite), and Varroa destructor(honey bee mite).

In another embodiment, the invention disclosed in this document can beused to control Nematoda (nematodes). A non-exhaustive list of thesepests includes, but is not limited to, Aphelenchoides spp. (bud and leaf& pine wood nematodes), Belonolaimus spp. (sting nematodes),Criconemella spp. (ring nematodes), Dirofilaria immitis (dog heartworm),Ditylenchus spp. (stem and bulb nematodes), Heterodera spp. (cystnematodes), Heterodera zeae (corn cyst nematode), Hirschmanniella spp.(root nematodes), Hoplolaimus spp. (lance nematodes), Meloidogyne spp.(root knot nematodes), Meloidogyne incognita (root knot nematode),Onchocerca volvulus (hook-tail worm), Pratylenchus spp. (lesionnematodes), Radopholus spp. (burrowing nematodes), and Rotylenchusreniformis (kidney-shaped nematode).

In another embodiment, the invention disclosed in this document can beused to control Symphyla (symphylans). A non-exhaustive list of thesepests includes, but is not limited to, Scutigerella immaculata.

For more detailed information consult “HANDBOOK OF PEST CONTROL—THEBEHAVIOR, LIFE HISTORY, AND CONTROL OF HOUSEHOLD PESTS” by ArnoldMallis, 9th Edition, copyright 2004 by GIE Media Inc.

Mixtures

The invention disclosed in this document can also be used with variousinsecticides, both for reasons of economy and synergy. Such insecticidesinclude, but are not limited to, antibiotic insecticides, macrocycliclactone insecticides (for example, avermectin insecticides, milbemycininsecticides, and spinosyn insecticides), arsenical insecticides,botanical insecticides, carbamate insecticides (for example,benzofuranyl methylcarbamate insecticides, dimethylcarbamateinsecticides, oxime carbamate insecticides, and phenyl methylcarbamateinsecticides), diamide insecticides, desiccant insecticides,dinitrophenol insecticides, fluorine insecticides, formamidineinsecticides, fumigant insecticides, inorganic insecticides, insectgrowth regulators (for example, chitin synthesis inhibitors, juvenilehormone mimics, juvenile hormones, moulting hormone agonists, moultinghormones, moulting inhibitors, precocenes, and other unclassified insectgrowth regulators), nereistoxin analogue insecticides, nicotinoidinsecticides (for example, nitroguanidine insecticides, nitromethyleneinsecticides, and pyridylmethylamine insecticides), organochlorineinsecticides, organophosphorus insecticides, oxadiazine insecticides,oxadiazolone insecticides, phthalimide insecticides, pyrazoleinsecticides, pyrethroid insecticides, pyrimidinamine insecticides,pyrrole insecticides, tetramic acid insecticides, tetronic acidinsecticides, thiazole insecticides, thiazolidine insecticides, thioureainsecticides, urea insecticides, as well as, other unclassifiedinsecticides.

Some of the particular insecticides that can be employed beneficially incombination with the invention disclosed in this document include, butare not limited to, the following 1,2-dichloropropane,1,3-dichloropropene, abamectin, acephate, acetamiprid, acethion,acetoprole, acrinathrin, acrylonitrile, alanycarb, aldicarb, aldoxycarb,aldrin, allethrin, allosamidin, allyxycarb, alpha-cypermethrin,alpha-endosulfan, amidithion, aminocarb, amiton, amitraz, anabasine,athidathion, azadirachtin, azamethiphos, azinphos-ethyl,azinphos-methyl, azothoate, barium hexafluorosilicate, barthrin,bendiocarb, benfuracarb, bensultap, beta-cyfluthrin, beta-cypermethrin,bifenthrin, bioallethrin, bioethanomethrin, biopermethrin,bioresmethrin, bistrifluron, borax, boric acid, boric acid,bromfenvinfos, bromocyclen, bromo-DDT, bromophos, bromophos-ethyl,bufencarb, buprofezin, butacarb, butathiofos, butocarboxim, butonate,butoxycarboxim, cadusafos, calcium arsenate, calcium polysulfide,camphechlor, carbanolate, carbaryl, carbofuran, carbon disulfide, carbontetrachloride, carbophenothion, carbosulfan, cartap,chlorantraniliprole, chlorbicyclen, chlordane, chlordecone,chlordimeform, chlorethoxyfos, chlorfenapyr, chlorfenvinphos,chlorfluazuron, chlormephos, chloroform, chloropicrin, chlorphoxim,chlorprazophos, chlorpyrifos, chlorpyrifos-methyl, chlorthiophos,chromafenozide, cinerin I, cinerin II, cismethrin, cloethocarb,closantel, clothianidin, copper acetoarsenite, copper arsenate, coppernaphthenate, copper oleate, coumaphos, coumithoate, crotamiton,crotoxyphos, crufomate, cryolite, cyanofenphos, cyanophos, cyanthoate,cyantraniliprole, cyclethrin, cycloprothrin, cyfluthrin, cyhalothrin,cypermethrin, cyphenothrin, cyromazine, cythioate, DDT, decarbofuran,deltamethrin, demephion, demephion-O, demephion-S, demeton,demeton-methyl, demeton-O, demeton-O-methyl, demeton-S,demeton-S-methyl, demeton-S-methylsulphon, diafenthiuron, dialifos,diatomaceous earth, diazinon, dicapthon, dichlofenthion, dichlorvos,dicresyl, dicrotophos, dicyclanil, dieldrin, diflubenzuron, dilor,dimefluthrin, dimefox, dimetan, dimethoate, dimethrin, dimethylvinphos,dimetilan, dinex, dinoprop, dinosam, dinotefuran, diofenolan,dioxabenzofos, dioxacarb, dioxathion, disulfoton, dithicrofos,d-limonene, DNOC, doramectin, ecdysterone, emamectin, EMPC, empenthrin,endosulfan, endothion, endrin, EPN, epofenonane, eprinomectin,esfenvalerate, etaphos, ethiofencarb, ethion, ethiprole, ethoate-methyl,ethoprophos, ethyl formate, ethyl-DDD, ethylene dibromide, ethylenedichloride, ethylene oxide, etofenprox, etrimfos, EXD, famphur,fenamiphos, fenazaflor, fenchlorphos, fenethacarb, fenfluthrin,fenitrothion, fenobucarb, fenoxacrim, fenoxycarb, fenpirithrin,fenpropathrin, fensulfothion, fenthion, fenthion-ethyl, fenvalerate,fipronil, flonicamid, flubendiamide, flucofuron, flucycloxuron,flucythrinate, flufenerim, flufenoxuron, flufenprox, fluvalinate,fonofos, formetanate, formothion, formparanate, fosmethilan, fospirate,fosthietan, furathiocarb, furethrin, gamma-cyhalothrin, gamma-HCH,halfenprox, halofenozide, HCH, HEOD, heptachlor, heptenophos,heterophos, hexaflumuron, HHDN, hydramethylnon, hydrogen cyanide,hydroprene, hyquincarb, imidacloprid, imiprothrin, indoxacarb,iodomethane, IPSP, isazofos, isobenzan, isocarbophos, isodrin,isofenphos, isoprocarb, isoprothiolane, isothioate, isoxathion,ivermectin, jasmolin I, jasmolin II, jodfenphos, juvenile hormone I,juvenile hormone II, juvenile hormone III, kelevan, kinoprene,lambda-cyhalothrin, lead arsenate, lepimectin, leptophos, lindane,lirimfos, lufenuron, lythidathion, malathion, malonoben, mazidox,mecarbam, mecarphon, menazon, mephosfolan, mercurous chloride,mesulfenfos, metaflumizone, methacrifos, methamidophos, methidathion,methiocarb, methocrotophos, methomyl, methoprene, methoxychlor,methoxyfenozide, methyl bromide, methylchloroform, methylene chloride,metofluthrin, metolcarb, metoxadiazone, mevinphos, mexacarbate,milbemectin, milbemycin oxime, mipafox, mirex, monocrotophos,morphothion, moxidectin, naftalofos, naled, naphthalene, nicotine,nifluridide, nitenpyram, nithiazine, nitrilacarb, novaluron,noviflumuron, omethoate, oxamyl, oxydemeton-methyl, oxydeprofos,oxydisulfoton, para-dichlorobenzene, parathion, parathion-methyl,penfluron, pentachlorophenol, permethrin, phenkapton, phenothrin,phenthoate, phorate, phosalone, phosfolan, phosmet, phosnichlor,phosphamidon, phosphine, phoxim, phoxim-methyl, pirimetaphos,pirimicarb, pirimiphos-ethyl, pirimiphos-methyl, potassium arsenite,potassium thiocyanate, pp′-DDT, prallethrin, precocene I, precocene II,precocene III, primidophos, profenofos, profluthrin, promacyl,promecarb, propaphos, propetamphos, propoxur, prothidathion, prothiofos,prothoate, protrifenbute, pyraclofos, pyrafluprole, pyrazophos,pyresmethrin, pyrethrin I, pyrethrin II, pyridaben, pyridalyl,pyridaphenthion, pyrifluquinazon, pyrimidifen, pyrimitate, pyriprole,pyriproxyfen, quassia, quinalphos, quinalphos-methyl, quinothion,rafoxanide, resmethrin, rotenone, ryania, sabadilla, schradan,selamectin, silafluofen, silica gel, sodium arsenite, sodium fluoride,sodium hexafluorosilicate, sodium thiocyanate, sophamide, spinetoram,spinosad, spiromesifen, spirotetramat, sulcofuron, sulfoxaflor,sulfluramid, sulfotep, sulfuryl fluoride, sulprofos, taufluvalinate,tazimcarb, TDE, tebufenozide, tebufenpyrad, tebupirimfos, teflubenzuron,tefluthrin, temephos, TEPP, terallethrin, terbufos, tetrachloroethane,tetrachlorvinphos, tetramethrin, theta-cypermethrin, thiacloprid,thiamethoxam, thicrofos, thiocarboxime, thiocyclam, thiodicarb,thiofanox, thiometon, thiosultap, thuringiensin, tolfenpyrad,tralomethrin, transfluthrin, transpermethrin, triarathene, triazamate,triazophos, trichlorfon, trichlormetaphos-3, trichloronat, trifenofos,triflumuron, trimethacarb, triprene, vamidothion, vaniliprole, XMC,xylylcarb, zeta-cypermethrin, zolaprofos, and α-ecdysone.

Additionally, any combination of the above insecticides can be used.

The invention disclosed in this document can also be used, for reasonsof economy and synergy, with acaricides, algicides, antifeedants,avicides, bactericides, bird repellents, chemosterilants, fungicides,herbicide safeners, herbicides, insect attractants, insect repellents,mammal repellents, mating disrupters, molluscicides, plant activators,plant growth regulators, rodenticides, synergists, defoliants,desiccants, disinfectants, semiochemicals, and virucides (thesecategories not necessarily mutually exclusive).

For more information consult “COMPENDIUM OF PESTICIDE COMMON NAMES”located at http://www.alanwood.net/pesticides/index.html. Also consult“THE PESTICIDE MANUAL” 14th Edition, edited by C D S Tomlin, copyright2006 by British Crop Production Council.

Synergistic Mixtures

The invention disclosed in this document can be used with othercompounds such as the ones mentioned under the heading “Mixtures” toform synergistic mixtures where the mode of action of the compounds inthe mixtures are the same, similar, or different.

Examples of mode of actions include, but are not limited to:acetylcholinesterase inhibitor; sodium channel modulator; chitinbiosynthesis inhibitor; GABA-gated chloride channel antagonist; GABA-and glutamate-gated chloride channel agonist; acetylcholine receptoragonist; MET I inhibitor; Mg-stimulated ATPase inhibitor; nicotinicacetylcholine receptor; Midgut membrane disrupter; oxidativephosphorylation disrupter, and ryanodine receptor (RyRs).

Additionally, the following compounds are known as synergists and can beused with the invention disclosed in this document: piperonyl butoxide,piprotal, propyl isome, sesamex, sesamolin, and sulfoxide.

Formulations

A pesticide is rarely suitable for application in its pure form. It isusually necessary to add other substances so that the pesticide can beused at the required concentration and in an appropriate form,permitting ease of application, handling, transportation, storage, andmaximum pesticide activity. Thus, pesticides are formulated into, forexample, baits, concentrated emulsions, dusts, emulsifiableconcentrates, fumigants, gels, granules, microencapsulations, seedtreatments, suspension concentrates, suspoemulsions, tablets, watersoluble liquids, water dispersible granules or dry flowables, wettablepowders, and ultra low volume solutions.

For further information on formulation types see “CATALOGUE OF PESTICIDEFORMULATION TYPES AND INTERNATIONAL CODING SYSTEM” Technical Monographn° 2, 5th Edition by CropLife International (2002).

Pesticides are applied most often as aqueous suspensions or emulsionsprepared from concentrated formulations of such pesticides. Suchwater-soluble, water-suspendable, or emulsifiable formulations, areeither solids, usually known as wettable powders, or water dispersiblegranules, or liquids usually known as emulsifiable concentrates, oraqueous suspensions. Wettable powders, which may be compacted to formwater dispersible granules, comprise an intimate mixture of thepesticide, a carrier, and surfactants. The concentration of thepesticide is usually from about 10% to about 90% by weight. The carrieris usually chosen from among the attapulgite clays, the montmorilloniteclays, the diatomaceous earths, or the purified silicates. Effectivesurfactants, comprising from about 0.5% to about 10% of the wettablepowder, are found among sulfonated lignins, condensednaphthalenesulfonates, naphthalenesulfonates, alkylbenzenesulfonates,alkyl sulfates, and nonionic surfactants such as ethylene oxide adductsof alkyl phenols.

Emulsifiable concentrates of pesticides comprise a convenientconcentration of a pesticide, such as from about 50 to about 500 gramsper liter of liquid dissolved in a carrier that is either a watermiscible solvent or a mixture of water-immiscible organic solvent andemulsifiers. Useful organic solvents include aromatics, especiallyxylenes and petroleum fractions, especially the high-boilingnaphthalenic and olefinic portions of petroleum such as heavy aromaticnaphtha. Other organic solvents may also be used, such as the terpenicsolvents including rosin derivatives, aliphatic ketones such ascyclohexanone, and complex alcohols such as 2-ethoxyethanol. Suitableemulsifiers for emulsifiable concentrates are chosen from conventionalanionic and nonionic surfactants.

Aqueous suspensions comprise suspensions of water-insoluble pesticidesdispersed in an aqueous carrier at a concentration in the range fromabout 5% to about 50% by weight. Suspensions are prepared by finelygrinding the pesticide and vigorously mixing it into a carrier comprisedof water and surfactants. Ingredients, such as inorganic salts andsynthetic or natural gums, may also be added, to increase the densityand viscosity of the aqueous carrier. It is often most effective togrind and mix the pesticide at the same time by preparing the aqueousmixture and homogenizing it in an implement such as a sand mill, ballmill, or piston-type homogenizer.

Pesticides may also be applied as granular compositions that areparticularly useful for applications to the soil. Granular compositionsusually contain from about 0.5% to about 10% by weight of the pesticide,dispersed in a carrier that comprises clay or a similar substance. Suchcompositions are usually prepared by dissolving the pesticide in asuitable solvent and applying it to a granular carrier which has beenpre-formed to the appropriate particle size, in the range of from about0.5 to about 3 mm. Such compositions may also be formulated by making adough or paste of the carrier and compound and crushing and drying toobtain the desired granular particle size.

Dusts containing a pesticide are prepared by intimately mixing thepesticide in powdered form with a suitable dusty agricultural carrier,such as kaolin clay, ground volcanic rock, and the like. Dusts cansuitably contain from about 1% to about 10% of the pesticide. They canbe applied as a seed dressing or as a foliage application with a dustblower machine.

It is equally practical to apply a pesticide in the form of a solutionin an appropriate organic solvent, usually petroleum oil, such as thespray oils, which are widely used in agricultural chemistry.

Pesticides can also be applied in the form of an aerosol composition. Insuch compositions the pesticide is dissolved or dispersed in a carrier,which is a pressure-generating propellant mixture. The aerosolcomposition is packaged in a container from which the mixture isdispensed through an atomizing valve.

Pesticide baits are formed when the pesticide is mixed with food or anattractant or both. When the pests eat the bait they also consume thepesticide. Baits may take the form of granules, gels, flowable powders,liquids, or solids. They are used in pest harborages.

Fumigants are pesticides that have a relatively high vapor pressure andhence can exist as a gas in sufficient concentrations to kill pests insoil or enclosed spaces. The toxicity of the fumigant is proportional toits concentration and the exposure time. They are characterized by agood capacity for diffusion and act by penetrating the pest'srespiratory system or being absorbed through the pest's cuticle.Fumigants are applied to control stored product pests under gas proofsheets, in gas sealed rooms or buildings or in special chambers.

Pesticides can be microencapsulated by suspending the pesticideparticles or droplets in plastic polymers of various types. By alteringthe chemistry of the polymer or by changing factors in the processing,microcapsules can be formed of various sizes, solubility, wallthicknesses, and degrees of penetrability. These factors govern thespeed with which the active ingredient within is released, which inturn, affects the residual performance, speed of action, and odor of theproduct.

Oil solution concentrates are made by dissolving pesticide in a solventthat will hold the pesticide in solution. Oil solutions of a pesticideusually provide faster knockdown and kill of pests than otherformulations due to the solvents themselves having pesticidal action andthe dissolution of the waxy covering of the integument increasing thespeed of uptake of the pesticide. Other advantages of oil solutionsinclude better storage stability, better penetration of crevices, andbetter adhesion to greasy surfaces.

Another embodiment is an oil-in-water emulsion, wherein the emulsioncomprises oily globules which are each provided with a lamellar liquidcrystal coating and are dispersed in an aqueous phase, wherein each oilyglobule comprises at least one compound which is agriculturally active,and is individually coated with a monolamellar or oligolamellar layercomprising: (1) at least one nonionic lipophilic surface-active agent,(2) at least one nonionic hydrophilic surface-active agent and (3) atleast one ionic surface-active agent, wherein the globules having a meanparticle diameter of less than 800 nanometers. Further information onthe embodiment is disclosed in U.S. patent publication 20070027034published Feb. 1, 2007, having patent application Ser. No. 11/495,228.For ease of use this embodiment will be referred to as “OIWE”.

For further information consult “INSECT PEST MANAGEMENT” 2nd Edition byD. Dent, copyright CAB International (2000). Additionally, for moredetailed information consult “HANDBOOK OF PEST CONTROL—THE BEHAVIOR,LIFE HISTORY, AND CONTROL OF HOUSEHOLD PESTS” by Arnold Mallis, 9thEdition, copyright 2004 by GIE Media Inc.

Other Formulation Components

Generally, the invention disclosed in this document when used in aformulation, such formulation can also contain other components. Thesecomponents include, but are not limited to, (this is a non-exhaustiveand non-mutually exclusive list) wetters, spreaders, stickers,penetrants, buffers, sequestering agents, drift reduction agents,compatibility agents, anti-foam agents, cleaning agents, andemulsifiers. A few components are described forthwith.

A wetting agent is a substance that when added to a liquid increases thespreading or penetration power of the liquid by reducing the interfacialtension between the liquid and the surface on which it is spreading.Wetting agents are used for two main functions in agrochemicalformulations: during processing and manufacture to increase the rate ofwetting of powders in water to make concentrates for soluble liquids orsuspension concentrates; and during mixing of a product with water in aspray tank to reduce the wetting time of wettable powders and to improvethe penetration of water into water-dispersible granules. Examples ofwetting agents used in wettable powder, suspension concentrate, andwater-dispersible granule formulations are: sodium lauryl sulfate;sodium dioctyl sulfosuccinate; alkyl phenol ethoxylates; and aliphaticalcohol ethoxylates.

A dispersing agent is a substance which adsorbs onto the surface of aparticles and helps to preserve the state of dispersion of the particlesand prevents them from reaggregating. Dispersing agents are added toagrochemical formulations to facilitate dispersion and suspension duringmanufacture, and to ensure the particles redisperse into water in aspray tank. They are widely used in wettable powders, suspensionconcentrates and water-dispersible granules. Surfactants that are usedas dispersing agents have the ability to adsorb strongly onto a particlesurface and provide a charged or steric barrier to reaggregation ofparticles. The most commonly used surfactants are anionic, nonionic, ormixtures of the two types. For wettable powder formulations, the mostcommon dispersing agents are sodium lignosulfonates. For suspensionconcentrates, very good adsorption and stabilization are obtained usingpolyelectrolytes, such as sodium naphthalene sulfonate formaldehydecondensates. Tristyrylphenol ethoxylate phosphate esters are also used.Nonionics such as alkylarylethylene oxide condensates and EO—PO blockcopolymers are sometimes combined with anionics as dispersing agents forsuspension concentrates. In recent years, new types of very highmolecular weight polymeric surfactants have been developed as dispersingagents. These have very long hydrophobic ‘backbones’ and a large numberof ethylene oxide chains forming the ‘teeth’ of a ‘comb’ surfactant.These high molecular weight polymers can give very good long-termstability to suspension concentrates because the hydrophobic backboneshave many anchoring points onto the particle surfaces. Examples ofdispersing agents used in agrochemical formulations are: sodiumlignosulfonates; sodium naphthalene sulfonate formaldehyde condensates;tristyrylphenol ethoxylate phosphate esters; aliphatic alcoholethoxylates; alkyl ethoxylates; EO—PO block copolymers; and graftcopolymers.

An emulsifying agent is a substance which stabilizes a suspension ofdroplets of one liquid phase in another liquid phase. Without theemulsifying agent the two liquids would separate into two immiscibleliquid phases. The most commonly used emulsifier blends containalkylphenol or aliphatic alcohol with twelve or more ethylene oxideunits and the oil-soluble calcium salt of dodecylbenzenesulfonic acid. Arange of hydrophile-lipophile balance (“HLB”) values from 8 to 18 willnormally provide good stable emulsions. Emulsion stability can sometimesbe improved by the addition of a small amount of an EO—PO blockcopolymer surfactant.

A solubilizing agent is a surfactant which will form micelles in waterat concentrations above the critical micelle concentration. The micellesare then able to dissolve or solubilize water-insoluble materials insidethe hydrophobic part of the micelle. The type of surfactants usuallyused for solubilization are nonionics: sorbitan monooleates; sorbitanmonooleate ethoxylates; and methyl oleate esters.

Surfactants are sometimes used, either alone or with other additivessuch as mineral or vegetable oils as adjuvants to spray-tank mixes toimprove the biological performance of the pesticide on the target. Thetypes of surfactants used for bioenhancement depend generally on thenature and mode of action of the pesticide. However, they are oftennonionics such as: alkyl ethoxylates; linear aliphatic alcoholethoxylates; aliphatic amine ethoxylates.

A carrier or diluent in an agricultural formulation is a material addedto the pesticide to give a product of the required strength. Carriersarc usually materials with high absorptive capacities, while diluentsare usually materials with low absorptive capacities. Carriers anddiluents are used in the formulation of dusts, wettable powders,granules and water-dispersible granules.

Organic solvents are used mainly in the formulation of emulsifiableconcentrates, ULV (ultra low volume) formulations, and to a lesserextent granular formulations. Sometimes mixtures of solvents are used.The first main groups of solvents are aliphatic paraffinic oils such askerosene or refined paraffins. The second main group and the most commoncomprises the aromatic solvents such as xylene and higher molecularweight fractions of C9 and C10 aromatic solvents. Chlorinatedhydrocarbons are useful as cosolvents to prevent crystallization ofpesticides when the formulation is emulsified into water. Alcohols aresometimes used as cosolvents to increase solvent power.

Thickeners or gelling agents are used mainly in the formulation ofsuspension concentrates, emulsions and suspoemulsions to modify therheology or flow properties of the liquid and to prevent separation andsettling of the dispersed particles or droplets. Thickening, gelling,and anti-settling agents generally fall into two categories, namelywater-insoluble particulates and water-soluble polymers. It is possibleto produce suspension concentrate formulations using clays and silicas.Examples of these types of materials, include, but are limited to,montmorillonite, e.g. bentonite; magnesium aluminum silicate; andattapulgite. Water-soluble polysaccharides have been used asthickening-gelling agents for many years. The types of polysaccharidesmost commonly used are natural extracts of seeds and seaweeds or aresynthetic derivatives of cellulose. Examples of these types of materialsinclude, but are not limited to, guar gum; locust bean gum; carrageenam;alginates; methyl cellulose; sodium carboxymethyl cellulose (SCMC);hydroxyethyl cellulose (HEC). Other types of anti-settling agents arebased on modified starches, polyacrylates, polyvinyl alcohol andpolyethylene oxide. Another good anti-settling agent is xanthan gum.

Microorganisms cause spoilage of formulated products. Thereforepreservation agents are used to eliminate or reduce their effect.Examples of such agents include, but are not limited to: propionic acidand its sodium salt; sorbic acid and its sodium or potassium salts;benzoic acid and its sodium salt; p-hydroxybenzoic acid sodium salt;methyl p-hydroxybenzoate; and 1,2-benzisothiazalin-3-one (BIT).

The presence of surfactants, which lower interfacial tension, oftencauses water-based formulations to foam during mixing operations inproduction and in application through a spray tank. In order to reducethe tendency to foam, anti-foam agents are often added either during theproduction stage or before filling into bottles. Generally, there aretwo types of anti-foam agents, namely silicones and non-silicones.Silicones are usually aqueous emulsions of dimethyl polysiloxane whilethe non-silicone anti-foam agents are water-insoluble oils, such asoctanol and nonanol, or silica. In both cases, the function of theanti-foam agent is to displace the surfactant from the air-waterinterface.

For further information, see “CHEMISTRY AND TECHNOLOGY OF AGROCHEMICALFORMULATIONS” edited by D. A. Knowles, copyright 1998 by Kluwer AcademicPublishers. Also see “INSECTICIDES IN AGRICULTURE AND ENVIRONMENT—RETROSPECTS AND PROSPECTS” by A. S. Perry, I. Yamamoto, I. Ishaaya, andR. Perry, copyright 1998 by Springer-Verlag.

Applications

The actual amount of pesticide to be applied to loci of pests isgenerally not critical and can readily be determined by those skilled inthe art. In general, concentrations from about 0.01 grams of pesticideper hectare to about 5000 grams of pesticide per hectare are expected toprovide good control.

The locus to which a pesticide is applied can be any locus inhabited byan pest, for example, vegetable crops, fruit and nut trees, grape vines,ornamental plants, domesticated animals, the interior or exteriorsurfaces of buildings, and the soil around buildings. Controlling pestsgenerally means that pest populations, activity, or both, are reduced ina locus. This can come about when: pest populations are repulsed from alocus; when pests are incapacitated in or around a locus; or pests areexterminated, in whole or in part, in or around a locus. Of course acombination of these results can occur. Generally, pest populations,activity, or both are desirably reduced more than fifty percent,preferably more than 90 percent.

Generally, with baits, the baits are placed in the ground where, forexample, termites can come into contact with the bait. Baits can also beapplied to a surface of a building, (horizontal, vertical, or slantsurface) where, for example, ants, termites, cockroaches, and flies, cancome into contact with the bait.

Because of the unique ability of the eggs of some pests to resistpesticides repeated applications may be desirable to control newlyemerged larvae.

Systemic movement of pesticides in plants may be utilized to controlpests on one portion of the plant by applying the pesticides to adifferent portion of the plant. For example, control of foliar-feedinginsects can be controlled by drip irrigation or furrow application, orby treating the seed before planting. Seed treatment can be applied toall types of seeds, including those from which plants geneticallytransformed to express specialized traits will germinate. Representativeexamples include those expressing proteins toxic to invertebrate pests,such as Bacillus thuringiensis or other insecticidal toxins, thoseexpressing herbicide resistance, such as “Roundup Ready” seed, or thosewith “stacked” foreign genes expressing insecticidal toxins, herbicideresistance, nutrition-enhancement or any other beneficial traits.Furthermore, such seed treatments with the invention disclosed in thisdocument can further enhance the ability of a plant to better withstandstressful growing conditions. This results in a healthier, more vigorousplant, which can lead to higher yields at harvest time.

It should be readily apparent that the invention can be used with plantsgenetically transformed to express specialized traits, such as Bacillusthuringiensis or other insecticidal toxins, or those expressingherbicide resistance, or those with “stacked” foreign genes expressinginsecticidal toxins, herbicide resistance, nutrition-enhancement or anyother beneficial traits.

The invention disclosed in this document is suitable for controllingendoparasites and ectoparasites in the veterinary medicine sector or inthe field of animal keeping. Compounds are applied in a known manner,such as by oral administration in the form of, for example, tablets,capsules, drinks, granules, by dermal application in the form of, forexample, dipping, spraying, pouring on, spotting on, and dusting, and byparenteral administration in the form of, for example, an injection.

The invention disclosed in this document can also be employedadvantageously in livestock keeping, for example, cattle, sheep, pigs,chickens, and geese. Suitable formulations are administered orally tothe animals with the drinking water or feed. The dosages andformulations that are suitable depend on the species.

Before a pesticide can be used or sold commercially, such pesticideundergoes lengthy evaluation processes by various governmentalauthorities (local, regional, state, national, international).Voluminous data requirements are specified by regulatory authorities andmust be addressed through data generation and submission by the productregistrant or by another on the product registrant's behalf. Thesegovernmental authorities then review such data and if a determination ofsafety is concluded, provide the potential user or seller with productregistration approval. Thereafter, in that locality where the productregistration is granted and supported, such user or seller may use orsell such pesticide.

The headings in this document are for convenience only and must not beused to interpret any portion thereof.

TABLE 1 Synthesis mp ¹H NMR # Structure Method MS (° C.) (DMSO-d₆, δ)¹ 4

C 461 (M + H) 107- 114 10.50 (s, 1H), 9.42 (s, 1H), 8.16 (s, 1H), 8.14(d, J = 8.1 Hz, 2H), 7.80 (d, J = 9.0 Hz, 2H), 7.76 (d, J = 8.4 Hz, 2H),7.62 (d, J = 8.7 Hz, 2H), 3.60 (t, J = 4.5 Hz, 4H), 3.42 (t, J = 4.2 Hz,4H) 5

C 496 (M + H) 207- 220 11.64 (s, 1H), 9.57 (s, 1H), 8.88 (t, J = 5.6 Hz,1H), 8.63-8.50 (m, 1H), 8.20 (m, 5H), 8.13 (s, 1H), 8.00 (d, J = 8.6 Hz,2H), 7.94 (d, J = 8.4 Hz, 2H), 7.40-7.19 (m, 2H), 3.93 (dd, J = 13.2,7.0 Hz, 2H), 3.11 (t, J = 7.3 Hz, 2H) 6

C 512 (M + H) 211- 217 11.67 (s, 1H), 9.46 (s, 1H), 8.80 (br s, 2H),8.41-8.38 (m, 1H), 8.15 (d, J = 8.0 Hz, 2H), 8.10 (d, J = 8.0 Hz, 2H),7.93 (d, J = 8.0 Hz, 2H), 7.86-7.82 (m, 3H), 7.64 (d, J = 8.0 Hz, 2H),4.07-4.02 (m, 2H), 3.36 (t, J = 8.0 Hz, 2H) 7

C 403 (M + H) 237- 247 10.44 (s, 1H), 9.56 (s, 1H), 8.21 (d, J = 8.0 Hz,2H), 8.14 (d, J = 8.0 Hz, 2H), 8.02 (d, J = 8.0 Hz, 2H), 7.89 (d, J =8.0 Hz, 3H), 7.14 (t, J = 8.0 Hz, 1H), 3.25- 3.16 (m, 2H), 1.10 (t, J =8.0 Hz, 3H) 8

C 419 (M + H) 10.43 (s, 1H), 9.43 (s, 1H), 8.13-8.07 (m, 4H), 7.88 (d, J= 8.0 Hz, 3H), 7.63 (d, J = 12.0 Hz, 2H), 7.13 (t, J = 8.0 Hz, 1H),3.20- 3.16 (m, 2H), 1.10 (t, J = 8.0 Hz, 3H) 9

C 562 (M + H) 221- 227 11.64 (br s, 1H), 9.46 (s, 1H), 8.88 (t, J = 4.0Hz, 1H), 8.58 (d, J = 4.0 Hz, 1H), 8.17 (d, J = 8.0 Hz, 2H), 8.11 (d, J= 8.0 Hz, 3H), 7.93 (d, J = 8.0 Hz, 2H), 7.76 (td, J = 8.0, 1.7 Hz, 1H),7.64 (d, J = 8.0 Hz, 2H), 7.34 (d, J = 8.0 Hz, 1H), 7.28 (dd, J = 8.0,4.0 Hz, 1H), 3.92 (q, J = 8.0 Hz, 2H), 3.10 (t, J = 8.0 Hz, 2H) 10

C 501 (M + H) 194- 196 (CDCl₃) 9.65 (s, 1H), 9.12 (s, 1H), 8.60 (s, 1H),8.27 (d, J = 8.4 Hz, 2H), 7.90 (s, 1H), 7.81 (m, 4H), 7.62 (m, 2H), 7.41(d, J = 8.3 Hz, 2H), 7.15-7.09 (m, 2H) 11

C 435 (M + H) 151 dec (CDCl₃) 8.83 (s, 1H), 8.59 (s, 1H), 8.22 (d, J =8.4 Hz, 2H), 7.81 (d, J = 9.0 Hz, 2H), 7.74- 7.68 (m, 3H), 7.40 (d, J =8.5 Hz, 2H), 3.48 (s, 6H) 12

C 447 (M + H) 220- 225 (CDCl₃) 9.17 (s, 1H), 8.60 (s, 1H), 8.25 (d, J =8.4 Hz, 2H), 7.84-7.79 (m, 3H), 7.76 (d, J = 8.4 Hz, 2H), 7.56 (s, 1H),7.41 (d, J = 8.4 Hz, 2H), 6.08-5.96 (m, 1H), 5.30 (m, J = 13.7, 11.6,1.3 Hz, 2H), 4.43 (m, 2H) 13

C 421 (M + H) 239- 241 (CDCl₃) 9.20 (s, 1H), 8.60 (s, 1H), 8.24 (d, J =8.4 Hz, 2H), 7.79 (m, 5H), 7.52 (s, 1H), 7.41 (d, J = 8.5 Hz, 2H), 3.30(s, J = 4.8 Hz, 3H) 14

C 483 (M + H) 215- 220 (CDCl₃) 9.47 (s, 1H), 9.23 (s, 1H), 8.60 (s, 1H),8.27 (d, J = 8.4 Hz, 2H), 7.91 (s, 1H), 7.81 (m, 4H), 7.70 (d, J = 7.6Hz, 2H), 7.43 (m, 4H), 7.29 (d, J = 7.4 Hz, 1H) 15

C 404 (M + H) 10.72 (s, 1H), 8.77 (s, 1H), 8.19 (d, J = 8.2 Hz, 2H),7.94 (s, 1H), 7.86 (d, J = 8.3 Hz, 2H), 7.78-7.64 (m, 4H), 7.58 (m, 1H),3.21 (d, J = 4.9 Hz, 3H) 16

B 520 (M + H) 207- 209 11.62 (s, 1H), 9.40 (s, 1H), 8.55 (br s, 1H),8.19- 8.06 (m, 5H), 7.92 (d, J = 8.2 Hz, 2H), 7.62 (d, J = 8.2 Hz, 2H),3.78-3.58 (m, 6H), 2.58- 2.42 (m, 6H) 17

B 528 (M + H) 178- 185 11.63 (s, 1H), 9.41 (s, 1H), 8.78 (br s, 1H),8.18-8.02 (m, 6H), 7.94 (d, J = 8.3 Hz, 2H), 7.68-7.58 (m, 3H), 6.99 (m,1H), 6.82 (m, 1H), 4.44 (t, J = 7.2 Hz, 2H), 3.98 (t, J = 7.1 Hz, 2H) 18

B 464 (M + H) 200- 203 9.82 (s, 1H), 8.61 (s, 1H), 8.21 (d, J = 8.3 Hz,2H), 7.89 (s, 1H), 7.82-7.78 (m, 3H), 7.74 (d, J = 8.3 Hz, 2H), 7.39 (d,J = 8.2 Hz, 2H), 3.97 (t, J = 7.2 Hz, 2H), 3.66 (t, J = 7.1 Hz, 2H),3.42 (s, 3H) 19

B 492 (M + H) 212- 215 11.57 (s, 1H), 9.42 (s, 1H), 8.88 (br s, 1H),8.18- 8.06 (m, 5H), 7.89 (d, J = 8.3 Hz, 2H), 7.63 (d, J = 8.3 Hz, 2H),3.64-3.57 (m, 2H), 2.38 (t, J = 7.3 Hz, 2H), 2.19 (s, 6H), 1.76 (t, J =7.1 Hz, 2H) 20

B 515 (M + H) 211- 215 11.59 (s, 1H), 9.40 (s, 1H), 8.42 (br s, 1H),8.17-8.02 (m, 5H), 7.91 (d, J = 8.2 Hz, 2H), 7.62 (d, J = 8.2 Hz, 2H),5.50 (br s, 1H), 3.68-3.59 (m, 2H), 2.22 (t, J = 7.2 Hz, 2H), 2.02- 1.87(m, 4H), 1.62-1.48 (m, 4H) 21

A 483 (M + H) 206- 210 12.04 (s, 1H), 10.32 (s, 1H), 9.42 (s, 1H), 8.68(m, 1H), 8.41 (m, 1H), 8.24-7.97 (m, 8H), 7.62 (d, J = 8.3 Hz, 2H), 7.42(m, 1H) 22

A 515 (M + H) 209- 211 11.78 (s, 1H), 9.41 (s, 1H), 9.18 (br s, 1H),8.18- 8.02 (m, 5H), 7.98 (d, J = 8.3 Hz, 2H), 7.62 (d, J = 8.3 Hz, 2H),7.38-7.22 (m, 2H), 7.20-7.17 (m, 2H), 4.89 (br s, 2H) 23

A 446 220- 222 11.60 (s, 1H), 9.44 (s, 1H), 8.39 (br s, 1H), 8.18- 8.02(m, 5H), 7.96 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.3 Hz, 2H), 3.08 (m,1H), 0.78 (m, 4H) 24

A 477 (M + H) 221- 224 11.43 (s, 1H), 9.39 (s, 1H), 8.58 (br s, 1H),8.14-7.99 (m, 5H), 7.95 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.2 Hz, 2H),3.59-3.49 (m, 2H), 1.68- 1.55 (m, 2H), 1.39-1.22 (m, 4H), 0.98 (t, J =7.2 Hz, 3H) 25

A 489 (M + H) 208- 210 11.48 (s, 1H), 9.42 (s, 1H), 8.18-8.04 (m, 5H),7.92 (d, J = 8.2 Hz, 2H), 7.61 (d, J = 8.3 Hz, 2H), 4.24- 4.18 (m, 1H),1.91-1.87 (m, 2H), 1.84- 1.76 (m, 2H), 1.74-1.62 (m, 2H), 1.60- 1.44 (m,2H), 1.43-1.18 (m, 2H) 26

A 566 204- 206 11.99 (s, 1H), 10.24 (s, 1H), 9.41 (s, 1H), 8.22 (s, 1H),8.18-8.00 (m, 6H), 7.67 (d, J = 8.2 Hz, 2H), 7.58 (d, J = 8.3 Hz, 2H),7.37 (d, J = 8.2 Hz, 2H) 27

A 486 213- 217 11.71 (s, 1H), 9.44 (s, 1H), 9.06 (br s, 1H), 8.18- 8.03(m, 5H), 7.97 (d, J = 8.2 Hz, 2H), 7.64-7.58 (m, 3H), 6.41 (m, 1H), 6.28(m, 1H), 4.83 (d, J = 6.0 Hz, 2H) 28

A 513 (M + H) 208- 210 11.82 (s, 1H), 10.06 (s, 1H), 9.42 (s, 1H), 8.20(s, 1H), 8.18-8.01 (m, 6H), 7.62 (d, J = 8.2 Hz, 2H), 7.39 (d, J = 8.2Hz, 2H), 6.94 (d, J = 8.2 Hz, 2H), 3.78 (s, 3H) 29

A 551 209- 211 12.06 (s, 1H), 10.19 (s, 1H), 9.42 (s, 1H), 8.22 (s, 1H),8.17-8.03 (m, 5H), 7.66- 7.57 (m, 4H), 7.42-7.38 (m, 2H) 30

A 492 233- 235 11.82 (s, 1H), 9.42 (s, 1H), 8.89 (br s, 1H), 8.17- 8.05(m, 5H), 7.96 (d, J = 8.3 Hz, 2H), 7.64 (d, J = 8.3 Hz, 2H), 4.34 (d, J= 6.2 Hz, 2H), 4.17 (q, J = 7.3 Hz, 2H), 1.22 (t, J = 7.1 Hz, 3H) 31

A 555 154- 157 12.78 (s, 1H), 11.32 (s, 1H), 9.39 (s, 1H), 8.38-8.02 (m,9H), 7.61- 7.54 (m, 4H) 32

A 550 228- 230 12.12 (s, 1H), 10.38 (s, 1H), 9.44 (s, 1H), 8.26 (s, 1H),8.18 (d, J = 8.3 Hz, 2H), 8.14-8.03 (m, 4H), 7.92 (d, J = 8.2 Hz, 2H),7.61 (d, J = 8.3 Hz, 2H), 7.64 (d, J = 8.2 Hz, 2H) 33

A 525 (M + H) 233- 236 12.12 (s, 1H), 10.38 (s, 1H), 9.43 (s, 1H), 8.24(s, 1H), 8.12 (d, J = 8.2 Hz, 2H), 8.10-8.02 (m, 4H), 7.96 (d, J = 8.3Hz, 2H), 7.82 (d, J = 8.3 Hz, 2H), 7.61 (d, J = 8.2 Hz, 2H), 2.58 (s,3H) 34

A 531 (M + H) 230- 232 11.72 (s, 1H), 9.41 (s, 1H), 9.18 (br s, 1H),8.16- 8.02 (m, 5H), 7.97 (d, J = 8.3 Hz, 2H), 7.63 (d, J = 8.3 Hz, 2H),7.38 (m, 4H), 4.84 (d, J = 6.2 Hz, 2H) 35

A 484 (M + H) 221- 224 10.82 (s, 1H), 9.43 (s, 1H), 9.04 (s, 1H),8.18-7.97 (m, 7H), 7.69- 7.58 (m, 4H), 7.18-7.06 (m, 2H) 36

A 576 (M + H) 200- 203 11.78 (s, 1H), 9.98 (s, 1H), 9.42 (s, 1H),8.19-8.02 (m, 7H), 7.64 (d, J = 8.2 Hz, 2H), 7.28 (d, J = 8.2 Hz, 2H),6.73 (d, J = 8.2 Hz, 2H), 2.91 (s, 6H) 37

B 540 (M + H) 193- 196 11.61 (s, 1H), 9.42 (s, 1H), 9.00 (br s, 1H),8.17- 8.04 (m, 5H), 7.94 (d, J = 8.3 Hz, 2H), 7.63 (d, J = 8.3 Hz, 2H),7.22 (d, J = 8.3 Hz, 2H), 6.65 (d, J = 8.2 Hz, 2H), 4.74 (d, J = 6.0 Hz,2H), 2.86 (s, 6H) 38

B 540 (M + H) 181- 183 11.64 (s, 1H), 9.41 (s, 1H), 9.08 (br s, 1H),8.18- 8.02 (m, 4H), 7.97 (d, J = 8.3 Hz, 2H), 7.62 (d, J = 8.3 Hz, 2H),7.16 (m, 2H), 6.78 (br s, 1H), 6.64- 6.55 (m, 2H), 4.79 (d, J = 6.0 Hz,2H), 2.84 (s, 6H) 39

B 540 (M + H) 165- 167 11.74 (s, 1H), 9.41 (s, 1H), 9.18 (br s, 1H),8.17-8.04 (m, 4H), 7.93 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.3 Hz, 2H),7.24- 7.18 (m, 4H), 7.03 (m, 1H), 4.92 (d, J = 6.2 Hz, 2H), 2.68 (s, 6H)40

B 554 (M + H) 153 dec 10.18 (s, 1H), 9.33 (s, 1H), 8.62 (s, 1H), 8.26(d, J = 8.2 Hz, 2H), 8.02 (s, 1H), 7.84-7.77 (m, 6H), 7.41 (d, J = 8.2Hz, 2H), 7.26 (d, J = 8.3 Hz, 2H), 3.31 (s, 3H), 1.97 (s, 3H) 41

B 540 (M + H) 205 dec 11.84 (s, 1H), 10.18 (s, 1H), 9.98 (s, 1H), 9.42(s, 1H), 8.19 (s, 1H), 8.17-8.03 (m, 6H), 7.66- 7.57 (m, 4H), 7.41 (d, J= 8.2 Hz, 2H), 2.04 (s, 3H) 42

B 512 (M + H) 196- 199 11.68 (s, 1H), 9.97 (s, 1H), 9.40 (s, 1H),8.19-7.99 (m, 7H), 7.62 (d, J = 8.3 Hz, 2H), 7.17 (d, J = 8.3 Hz, 2H),6.48 (d, J = 8.3 Hz, 2H), 5.63 (m, 1H), 2.64 (d, J = 4.9 Hz, 3H) 43

B 528 (M + H) 219- 222 12.02 (s, 1H), 10.03 (s, 1H), 9.42 (s, 1H), 8.38(s, 2H), 8.22-8.01 (m, 7H), 7.63 (d, J = 8.3 Hz, 2H), 3.17 (s, 6H) 44

B 541 (M + H) 206- 209 12.22 (s, 1H), 10.46 (s, 1H), 9.98 (s, 1H), 9.42(s, 1H), 8.84 (br s, 1H), 8.31- 8.18 (m, 3H), 8.12-8.04 (d, J = 8.2 Hz,2H), 7.98- 7.63 (m, 4H), 7.61 (d, J = 8.2 Hz, 2H), 2.06 (s, 3H) 45

B 543 (M + H) 193- 196 11.82 (s, 1H), 9.81 (s, 1H), 9.42 (s, 1H),8.21-8.14 (m, 3H), 8.08 (d, J = 8.3 Hz, 2H), 7.96 (d, J = 8.3 Hz, 2H),7.74 (m, 1H), 7.63 (d, J = 8.3 Hz, 2H), 6.64 (m, 1H), 6.57 (m, 1H), 3.82(s, 3H), 3.78 (s, 3H) 46

B 527 (M + H) 198- 201 11.81 (s, 1H), 9.96 (s, 1H), 9.41 (s, 1H), 8.18(s, 1H), 8.14-8.02 (m, 6H), 7.62 (d, J = 8.2 Hz, 2H), 7.18 (m, 1H), 6.84(m, 1H), 6.77 (m, 1H), 3.78 (s, 3H), 2.21 (s, 3H) 47

B 518 209- 211 12.20 (s, 1H), 9.89 (s, 1H), 9.43 (s, 1H), 8.22 (s, 1H),8.19-8.01 (m, 6H), 7.61 (d, J = 8.2 Hz, 2H), 7.48- 7.39 (m, 1H), 7.23(m, 2H) 48

B 640 198- 201 12.04 (s, 1H), 10.22 (s, 1H), 9.41 (s, 1H), 8.23 (s, 1H),8.18-8.04 (m, 6H), 7.76 (d, J = 8.2 Hz, 2H), 7.63 (d, J = 8.3 Hz, 2H),7.22 (m, 1H) 49

B 594 (M + H) 205- 208 11.98 (s, 1H), 9.82 (s, 1H), 9.41 (s, 1H),8.19-7.96 (m, 7H), 7.62 (d, J = 8.2 Hz, 2H), 7.31 (m, 1H), 6.98 (m, 1H),6.84 (m, 1H), 2.99 (s, 6H) 50

B 531 (M + H) 198- 201 11.98 (s, 1H), 9.96 (s, 1H), 9.43 (s, 1H), 8.20(s, 1H), 8.17-8.03 (m, 6H), 7.63 (d, J = 8.3 Hz, 2H), 7.34 (m, 1H), 6.96(m, 1H), 6.78 (m, 1H), 3.78 (s, 3H) 51

B 581 (M + H) 205- 208 12.03 (s, 1H), 9.97 (s, 1H), 9.42 (s, 1H), 8.18(s, 1H), 8.16-8.01 (m, 6H), 7.62 (d, J = 8.3 Hz, 2H), 7.48 (m, 1H),7.33- 7.18 (m, 2H), 3.84 (s, 3H) 52

B 561 (M + H) 183- 186 9.42 (s, 1H), 8.42 (m, 1H), 8.24 (s, 1H), 8.18(d, J = 8.3 Hz, 2H), 8.16-8.04 (m, 5H), 7.99- 7.89 (m, 2H), 7.78 (m,1H), 7.62 (d, J = 8.3 Hz, 2H), 7.45 (m, 1H), 3.26 (s, 3H) 53

B 507 10.03 (s, 1H), 9.48 (s, 1H), 8.42 (d, J = 8.2 Hz, 2H), 8.37 (d, J= 8.2 Hz, 2H), 8.17-8.06 (m, 2H), 7.86- 7.75 (m, 4H), 7.71-7.54 (m, 4H)54

B 517 (M + H) 211- 214 12.08 (s, 1H), 10.18 (s, 1H), 9.43 (s, 1H), 8.21(s, 1H), 8.16-7.99 (m, 6H), 7.71-7.57 (m, 4H), 7.42- 7.28 (m, 2H) 55

B 551 215- 218 12.17 (s, 1H), 10.17 (s, 1H), 9.41 (s, 1H), 8.22 (s, 1H),8.17-7.98 (m, 6H), 7.74- 7.58 (m, 4H), 7.43 (m, 1H) 56

B 517 (M + H) 214- 217 11.98 (s, 1H), 10.22 (s, 1H), 9.41 (s, 1H), 8.21(s, 1H), 8.19-8.03 (m, 8H), 7.63 (d, J = 8.3 Hz, 2H), 7.42 (d, J = 8.3Hz, 2H) 57

B 543 (M + H) 197- 199 11.76 (s, 1H), 9.42 (s, 1H), 9.38 (s, 1H),8.17-8.01 (m, 7H), 7.61 (d, J = 8.3 Hz, 2H), 7.23 (m, 1H), 6.68 (d, J =8.3 Hz, 2H), 3.78 (s, 6H) 58

B 527 (M + H) 195- 197 11.81 (s, 1H), 10.07 (s, 1H), 9.42 (s, 1H), 8.19(s, 1H), 8.16-8.01 (m, 6H), 7.63 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.2Hz, 2H), 6.91 (d, J = 8.2 Hz, 2H), 4.04 (q, J = 7.3 Hz, 2H), 1.38 (t, J= 7.2 Hz, 3H) 59

B 518 (M + H) 202- 204 12.28 (s, 1H), 10.32 (s, 1H), 9.42 (s, 1H), 8.46(m, 1H), 8.24 (s, 1H), 8.21-7.96 (m, 8H), 7.63 (d, J = 8.2 Hz, 2H) 60

B 608 (M + H) 135 dec 10.86 (s, 1H), 10.04 (s, 1H), 9.41 (s, 1H), 8.18(d, J = 8.3 Hz, 2H), 8.14-8.02 (m, 3H), 7.84-7.78 (m, 3H), 7.62 (d, J =8.3 Hz, 2H), 7.42 (m, 1H), 7.33 (m, 1H), 7.12 (m, 1H) 61

B 579 (M + H) 128 dec (CDCl₃) 10.09 (s, 1H), 8.62 (m, 2H), 8.38 (d, J =8.2 Hz, 1H), 8.31 (d, J = 8.6 Hz, 2H), 8.01 (d, J = 8.5 Hz, 1H), 7.85-7.76 (m, 6H), 7.41 (m, 3H) 62

B 511 (M + H) 189- 194 (CDCl₃) 9.06 (s, 1H), 8.63 (s, 1H), 8.26 (d, J =8.4 Hz, 2H), 7.93 (s, 1H), 7.85-7.76 (m, 5H), 7.70 (s, 1H), 7.41 (d, J =9.0 Hz, 2H), 7.32- 7.27 (m, 3H), 2.73 (q, J = 7.6 Hz, 2H), 1.30 (t, J =7.6 Hz, 3H) 63

B 535 (M + H) 175- 187 11999688 (CDCl₃) 9.49 (s, 1H), 8.63 (d, J = 8.4Hz, 2H), 8.26 (d, J = 8.3 Hz, 2H), 7.91 (s, 1H), 7.86- 7.79 (m, 4H),7.41 (d, J = 8.1 Hz, 2H), 7.33 (d, J = 8.2 Hz, 2H) 64

B 573 (M + H) 190 dec 12.47 (s, 1H), 10.07 (s, 1H), 9.45 (s, 1H), 8.25(s, 1H), 8.23-8.02 (m, 6H), 7.64 (d, J = 8.4 Hz, 2H) 65

B 531 (M + H) 197- 205 (CDCl₃) 11.65 (s, 1H), 9.88 (s, 1H), 8.93 (dd, J= 8.2, 1.4 Hz, 1H), 8.70 (s, 1H), 8.24 (d, J = 8.4 Hz, 2H), 8.18 (s,1H), 7.89- 7.80 (m, J = 15.8, 8.7 Hz, 4H), 7.41 (d, J = 8.4 Hz, 2H),7.34-7.31 (m, 1H), 7.28-7.16 (m, 1H), 2.45 (s, 3H) 66

B 567 (M + H) 200- 210 (CDCl₃) 11.65 (s, 1H), 9.88 (s, 1H), 8.93 (dd, J= 8.2, 1.4 Hz, 1H), 8.70 (s, 1H), 8.24 (d, J = 8.4 Hz, 2H), 8.18 (s,1H), 7.89-7.79 (m, 5H), 7.45- 7.38 (m, J = 8.3 Hz, 3H), 7.21 (dd, J =8.4, 1.5 Hz, 1H) 67

C 513 (M + 2) 510 (M − 1) 199- 200 11.74 (br s, 1H), 10.87 (br s, 1H),10.04 (s, 1H), 8.43 (dd, J = 10.2, 1.2 Hz, 2H), 8.16 (s, 1H), 7.87-7.96(m, 6H), 7.60 (d, J = 8.1 Hz, 2H), 7.41 (d, J = 8.7 Hz, 2H), 6.95 (d, J= 9.0 Hz, 1H), 3.78 (s, 3H) 68

C 195- 196 12.02 (br s, 1H), 10.12 (br s, 1H), 8.46 (d, J = 1.5 Hz, 1H),8.42 (d, J = 1.2 Hz, 1H), 8.16 (s, 1H), 7.86- 7.96 (m, 6H), 7.60 (d, J =7.8 Hz, 2H), 7.57 (d, J = 7.8 Hz, 2H), 7.39 (dd, J = 8.7, 7.5 Hz, 1H) 69

C 495 209- 210 11.77 (br s, 1H), 10.10 (br s, 1H), 8.57 (s, 1H), 8.52(d, J = 1.5 Hz, 1H), 8.16 (s, 1H), 8.15 (d, J = 5.4 Hz, 2H), 8.06 (d, J= 4.8 Hz, 2H), 7.80 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 7.2 Hz, 2H), 7.37(d, J = 6.9 Hz, 2H), 6.92 (dd, J = 8.2, 2.1 Hz, 1H), 3.76 (s, 3H) 70

C 536 (M + 2) 535 (M + H) 218 219 12.07 (br s, 1H), 10.18 (br s, 1H),8.57 (d, J = 1.2 Hz, 1H), 8.52 (d, J = 1.2 Hz, 1H), 8.17 (s, 1H),8.05-8.17 (m, 4H), 7.80 (d, J = 8.4 Hz, 2H), 7.75 (d, J = 8.4 Hz, 2H),7.55 (d, J = 8.4 Hz, 2H), 7.39 (dd, J = 9.3 Hz, 1H) 71

B 189- 198 (CDCl₃) 9.57 (s, 1H), 9.02 (s, 1H), 8.60 (s, 1H), 8.26 (d, J= 8.3 Hz, 2H), 7.93 (s, 1H), 7.85 (m, 4H), 7.71 (d, J = 7.5 Hz, 1H),7.41 (d, J = 8.9 Hz, 2H), 7.34-7.24 (m, 3H), 2.39 (s, 3H) 72

B 198- 218 (CDCl₃) 9.55 (s, 1H), 8.70 (s, 1H), 8.60 (s, 1H), 8.3 (d, J =8.7 Hz, 2H), 7.9 (s, 1H), 7.85-7.7 (m, 4H), 7.4 (d, J = 8.4 Hz, 2H),7.25-7.20 (m, 3H), 2.75 (q, J = 7 Hz, 2H), 2.45 (s, 3H), 1.30 (t, J = 7Hz, 3H) 73

B 184- 190 (CDCl₃) 9.42 (s, 1H), 8.60 (s, 2H), 8.26 (d, J = 8.3 Hz, 2H),7.88 (s, 1H), 7.85- 7.74 (m, 4H), 7.41 (d, J = 8.8 Hz, 2H), 7.3-7.25 (m,1H), 6.92 (d J = 8.1 Hz, 1H), 6.85 (d J = 8.1 Hz, 1H), 3.85 (s, 3H),2.38 (s, 3H) 74

B 513 (M + 1) 195- 208 (CDCl₃) 9.00 (s, 1H), 8.85 (d, J = 8.2 Hz, 1H),8.60 (s, 1H), 8.28 (d, J = 8.4 Hz, 2H), 7.90- 7.75 (m, 5H), 7.41 (d, J =8.9 Hz, 2H), 7.26 (m, 1H), 7.17 (t, J = 7.8 Hz, 1H), 7.09- 6.92 (m, 2H),3.99 (s, 3H) 75

B 529 (M + H) 170- 230 dec (CDCl₃) 11.45 (s, 1H), 10.24 (s, 1H), 8.70(s, 1H), 8.62 (d, J = 8.1 Hz, 1H), 8.25 (d, J = 8.4 Hz, 2H), 8.16 (s,1H), 7.94- 7.81 (m, 4H), 7.59-7.09 (m, 5H), 2.45 (s, 3H) 76

B 539 (M + 1) 212- 219 (CDCl₃) 9.41 (s, 1H), 8.71 (s, 1H), 8.60 (s, 1H),8.26 (d, J = 8.3 Hz, 2H), 7.91 (s, 1H), 7.86-7.69 (m, 4H), 7.41 (d, J =8.8 Hz, 2H), 7.36- 7.16 (m, 3H), 2.71 (q, J = 7.6 Hz, 4H), 1.27 (t, J =7.6 Hz, 6H) 77

B 570 (M + 1) 213- 215 (CDCl₃) 11.11 (s, 1H), 9.16 (s, 1H), 8.71 (d, J =8.3 Hz, 2H), 8.60 (s, 1H), 8.29 (d, J = 8.3 Hz, 2H), 8.01-7.77 (m, 5H),7.66 (t, J = 7.9 Hz, 1H), 7.46-7.29 (m, 3H), 2.75 (s, 6H) 78

C 511 (M + 1) 220- 225 (CDCl₃) 9.30 (s, 1H), 8.69 (s, 1H), 8.60 (s, 1H),8.26 (d, J = 8.4 Hz, 2H), 7.89 (s, 1H), 7.81 (m, 4H), 7.41 (d, J = 8.4Hz, 2H), 7.19 (m, 3H), 2.35 (s, 6H) 79

B 496 (M + H) 206- 208 11.78 (s, 1H), 9.41 (s, 1H), 9.37 (s, 1H),8.22-7.99 (m, 6H), 7.63 (d, J = 8.26 Hz, 2H), 7.23 (m, 1H), 6.70 (d, J =8.24 Hz, 2H), 6.48 (m, 1H), 4.12-3.98 (m, 4H), 1.39- 1.22 (m, 6H) 80

B 525 (M + H) 168- 180 (CDCl₃) 10.2 (s, 1H), 9.07 (s, 1H), 8.63 (s, 1H),8.25 (d, J = 8.4 Hz, 2H), 8.0 (s, 1H), 7.9-7.7 (m, 4H), 7.65 (d, J = 8Hz, 1H), 7.4-7.25 (m, 5H), 3.25 (heptet, J = 7 Hz, 1H), 1.35 (d, J = 7Hz, 6H) 81

B 498 (M + H) 191- 195 11.72 (s, 1H), 9.96 (s, 1H), 9.42 (s, 1H),8.21-8.01 (m, 5H), 7.63 (d, J = 8.26 Hz, 2H), 7.08 (d, J = 8.22 Hz, 2H),6.58 (d, J = 8.22 Hz, 2H), 5.19 (br s, 2H) 82

B 184- 189 9.5 (br s, 1H), 9.11 (s, 1H), 8.61 (s, 1H), 8.27 (d, J = 8Hz, 2H), 7.92 (s, 1H), 7.81 (m, 5H), 7.41 (d, J = 8 Hz, 2H), 7.28 (m,3H), 2.67 (t, J = 8 Hz, 2H), 1.70 (m, 2H), 1.01 (t, J = 7.5 Hz, 3H) 83

B 536 (M − H) — (CDCl₃) 10.1 (s, 1H), 8.62 (s, 1H), 8.4 (s, 1H), 8.36(d, J = 8.4 Hz, 2H), 8.03 (d, J = 8.6 Hz, 2H), 7.85 (d, J = 8.4 Hz, 2H),7.45- 7.38 (m, 3H), 7.30-7.19 (m, 3H), 6.9 (d, J = 7 Ha, 1H), 1.50 (s,9H) 84

B 541 (M + 1) 160- 170 12.25 (s, 1H), 12.24 (s, 1H), 20117139.5 (s, 1H),9.23 (s, 1H), 8.4- 8.05 (m, 8H), 7.68 (m, 3H), 7.4 (t, J = 7 Hz, 1H),3.50 (s, 3H) 85

A 541 (M + H) 171- 173 10.22 (s, 1H), 9.41 (s, 1H), 8.23-8.04 (m, 7H),7.62 (d, J = 8.24 Hz, 2H), 7.10 (m, 1H), 6.83-6.77 (m, 2H), 3.96 (s,3H), 3.78 (s, 3H), 2.00 (s, 3H) 86

A 555 (M + H) 188- 190 10.17 (s, 1H), 9.42 (s, 1H), 8.23 (d, J = 8.26Hz, 2H), 8.17-8.03 (m, 5H), 7.63 (d, J = 8.24 Hz, 2H), 7.11 (m, 1H),6.85-6.76 (m, 2H), 4.68 (q, J = 7.26 Hz, 2H), 3.78 (s, 3H), 2.19 (s,3H), 1.24 (t, J = 7.36 Hz, 3H) 87

A 569 (M + H) 195- 197 10.18 (s, 1H), 9.41 (s, 1H), 8.23 (d, J = 8.26Hz, 2H), 8.17-8.05 (m, 5H), 7.63 (d, J = 8.24 Hz, 2H), 7.12 (m, 1H),6.86-6.78 (m, 2H), 4.61- 4.58 (m, 2H), 3.79 (s, 3H), 2.18 (s, 3H),1.76-1.60 (m, 2H), 1.01-0.97 (t, J = 7.38 Hz, 3H) 88

B 573 (M + 1) — 11.72 (s, 1H), 9.44 (s, 1H), 9.28 (s, 1H), 8.14-8.1 (m,7H), 7.63 (d, J = 8 Hz, 2H), 7.63 (s, 2H), 3.81 (s, 3H), 3.74 (s, 6H) 89

B 527 (M + H) 210- 217 11.96 (s, 1H), 10.0 (s, 1H), 9.42 (s, 1H),8.2-7.9 (m, 8H), 7.6 (d, J = 8.5 Hz, 2H), 6.96 (s, 2H), 3.85 (s, 3H),4.27 (s, 3H) 90

B 527 (M + H) 85 dec 11.85 (s, 1H), 10.04 (s, 1H), 9.41 (s, 1H), 8.19(s, 1H), 8.17-8.0 (m, 6H), 7.6 (d, J = 8.5 Hz, 2H), 7.17 (t, J = 7 Hz,1H), 6.9 (m, 2H), 3.80 (s, 3H), 2.03 (s, 3H) 91

B 523 (M + 1) 186- 194 11.93 (s, 1H), 10.0 (s, 1H), 9.44 (s, 1H), 8.18(d, J = 8.4 Hz, 2H), 8.15 (s, 1H), 8.10 (d, J = 9.1 Hz, 2H), 7.98 (d, J= 7.6 Hz, 2H), 7.74 (d, J = 7.6 Hz, 1H), 7.64 (d, J = 8.6 Hz, 2H),7.34-7.25 (m, 3H), 5.28 (s, 1H), 5.12 (s, 1H), 2.96 (s, 3H) 92

B 497 (M + 1) 204- 211 11.88 (s, 1H), 10.13 (s, 1H), 9.44 (s, 1H), 8.21(s, 1H), 8.15 (d, J = 8.4 Hz, 2H), 8.11-8.04 (m, 4H), 7.64 (d, J = 8.6Hz, 2H), 7.43 (d, J = 8.2 Hz, 2H), 7.19 (d, J = 8.2 Hz, 2H), 2.32 (s,3H) 93

B 525 (M + 1) 218- 225 (CDCl₃) 9.37 (s, 1H), 8.63 (s, 1H), 8.60 (s, 1H),8.26 (d, J = 8.4 Hz, 2H), 7.89 (s, 1H), 7.85- 7.76 (m, 4H), 7.41 (d, J =8.4 Hz, 2H), 6.97 (s, 2H), 2.32 (s, 3H), 2.30 (s, 6H) 94

B 513 (M + 1) 80 dec 11.94 (s, 1H), 10.15 (s, 1H), 9.44 (s, 1H), 8.22(s, 1H), 8.20-8.02 (m, 6H), 7.64 (d, J = 8.7 Hz, 2H), 7.28 (m, 2H), 7.19(d, J = 8.6 Hz, 1H), 6.80 (d, J = 6.5 Hz, 1H), 3.78 (s, 3H) 95

B 511 (M + 1) 201- 207 (CDCl₃) 9.26 (s, 1H), 8.92 (s, 1H), 8.60 (s, 1H),8.26 (d, J = 8.3 Hz, 2H), 7.88 (s, 1H), 7.84- 7.77 (m, 4H), 7.50 (d, J =7.8 Hz, 1H), 7.41 (m 2H), 7.14-7.07 (m, 2H), 2.36 (s, 3H), 2.34 (s, 3H)96

B 205 dec (CDCl₃) 9.82 (s, 1H), 8.60 (s, 1H), 8.26 (d, J = 8.3 Hz, 2H),7.96 (s, 1H), 7.85-7.75 (m, 5H), 7.40 (d, J = 8.8 Hz, 2H), 7.34-7.23 (m,2H), 7.16 (d, J = 7.2 Hz, 1H), 3.23-3.12 (m, 1H), 2.36 (s, 3H), 1.33 (d,J = 6.8 Hz, 3H), 1.23 (d, J = 6.9 Hz, 3H) 97

C 561 (M + H) 234- 238 (CDCl₃) 9.62 (s, 1H), 8.70 (s, 1H), 8.60 (s, 1H),8.26 (d, J = 8.4 Hz, 2H), 7.92 (s, 1H), 7.86-7.75 (m, 4H), 7.41 (d, J =9.0 Hz, 2H), 7.18 (m, 3H), 2.35 (s, 6H) 98

B 537 (M + H) 200- 205 12.2 (s, 1H), 10.85 (s, 1H), 9.39 (s, 1H), 8.20(s, 1H), 8.18-7.97 (m, 6H), 7.6 (d, J = 8.5 Hz, 2H), 7.45 (m, 2H) 99

B 190 dec 12.05 (s, 1H), 10.17 (s, 1H), 9.44 (s, 1H), 8.37 (d, J = 3.7Hz, 1H), 8.22 (s, 1H), 8.20-8.00 (m, 6H), 7.75-7.57 (m, 3H), 7.38- 7.24(m, 1H), 2.44 (s, 3H) 100

B 557 (M + 1) 213- 220 11.86 (s, 1H), 9.90 (s, 1H), 9.44 (s, 1H), 8.24(s, 1H), 8.20-7.98 (m, 6H), 7.63 (d, J = 8.5 Hz, 2H), 7.02 (s, 2H), 2.48(s, 3H), 2.18 (s, 6H) 101

B 545 (M + 1) 211- 217 11.97 (s, 1H), 10.07 (s, 1H), 9.44 (s, 1H), 8.20(s, 1H), 8.17-8.03 (m, 6H), 7.63 (d, J = 8.3 Hz, 2H), 7.34 (d, J = 8.3Hz, 1H), 7.17 (d, J = 8.3 Hz, 1H), 2.23 (s, 3H), 2.19 (s, 3H) 102

B 512 (M + 1) 193 dec 12.01 (s, 1H), 10.05 (s, 1H), 9.44 (s, 1H), 8.26(d, J = 4.9 Hz, 1H), 8.21 (s, 1H), 8.19-8.02 (m, 6H), 7.63 (d, J = 8.8Hz, 2H), 7.19 (d, J = 4.9 Hz, 1H), 2.38 (s, 3H), 2.22 (s, 3H) 103

B 541 (M + 1) 214- 219 11.77 (s, 1H), 9.59 (s, 1H), 9.44 (s, 1H), 8.23(s, 1H), 8.20-7.98 (m, 6H), 7.63 (d, J = 8.9 Hz, 2H), 6.74 (s, 1H), 6.68(s, 1H), 2.92 (s, 3H), 2.31 (s, 3H), 2.15 (s, 3H) 104

B 545 (M + H) 215- 220 11.91 (s, 1H), 9.93 (s, 1H), 9.40 (s, 1H), 8.2(s, 1H), 8.20-8.0 (m, 6H), 7.58 (d, J = 8.4 Hz, 2H), 7.20 (s, 1H), 7.02(s, 1H), 2.24 (s, 3H), 2.21 (s, 3H) 105

B  580, 582 (M + 1) 194- 209 (CDCl₃) 9.60 (s, 1H), 8.67 (s, 1H), 8.60(s, 1H), 8.27 (d, J = 8.3 Hz, 2H), 7.93 (s, 1H), 7.89-7.77 (m, 4H), 7.51(d, J = 8.2 Hz, 2H), 7.41 (d, J = 8.7 Hz, 2H), 7.20 (t, J = 8.7 Hz, 1H)106

B 526 (M + 1) 195- 207 11.97 (s, 1H), 9.96 (s, 1H), 9.40 (s, 1H), 8.21(s, 1H), 8.19-8.02 (m, 6H), 7.63 (d, J = 8.6 Hz, 2H), 7.0 (s, 1H), 2.38(s, 3H), 2.26 (s, 3H), 2.15 (s, 3H) 107

B 567 (M + H) 217- 224 11.80 (s, 1H), 9.85 (s, 1H), 9.40 (s, 1H), 8.2(s, 1H), 8.18-8.0 (m, 6H), 7.6 (d, J = 8.4 Hz, 2H), 7.5-7.1 (m, 3H),3.05 (m, 2H), 1.17 (m, 12H) 108

B 549 (M + H) 206- 213 12.14 (s, 1H), 10.88 (s, 1H), 10.42 (s, 1H), 8.22(s, 1H), 8.2-8.0 (m, 6H), 7.65 (d, J = 8.4 Hz, 2H), 6.87 (d, J = 9 Hz,2H), 3.82 (s, 3H) 109

C 541 (M + H) 198- 201 10.57 (s, 1H), 9.84 (s, 1H), 9.41 (s, 1H), 8.21(d, J = 8.26 Hz, 2H), 8.17-8.03 (m, 4H), 7.63 (d, J = 8.26 Hz, 2H), 7.18(m, 1H), 6.87-6.77 (m, 2H), 3.77 (s, 3H), 2.41 (s, 3H), 2.24 (s, 3H) 110

C 553 (M + H) 208- 213 9.86 (s, 1H), 9.41 (s, 1H), 8.24 (d, J = 8.26 Hz,2H), 8.14-8.03 (m, 5H), 7.63 (d, J = 8.26 Hz, 2H), 7.27 (m, 1H),7.18-7.11 (m, 2H), 2.65- 2.57 (m, 4H), 2.41 (s, 3H), 1.24-1.09 (m, 6H)111

B 541 (M + H) 191- 194 11.82 (s, 1H), 9.96 (s, 1H), 9.42 (s, 1H),8.21-8.01 (m, 7H), 7.63 (d, J = 8.26 Hz, 2H), 7.13 (m, 1H), 6.84-6.78(m, 2H), 3.78 (s, 3H), 2.58 (q, J = 7.22 Hz, 2H), 1.97 (t, J = 9.40 Hz,3H) 112

B 529 (M + H) 214 dec 11.89 (s, 1H), 10.90 (s, 1H), 9.42 (s, 1H), 8.21(s, 1H), 8.2-8.0 (m, 6H), 7.6 (d, J = 8 4 Hz, 2H), 6.99 (d, J = 9 Hz,2H), 2.2 (s, 6H) 113

B 552 142- 162 dec 12.16 (s, 1H), 10.52 (s, 1H), 9.43 (s, 1H), 8.59 (s,1H), 8.40 (s, 1H), 8.25-8.0 (m, 7H), 7.6 (d, J = 8.4 Hz, 2H) 114

B 545 (M + H) 238- 245 11.89 (s, 1H), 9.90 (s, 1H), 9.42 (s, 1H), 8.21(s, 1H), 8.2-8.0 (m, 6H), 7.6 (d, J = 8 4 Hz, 2H), 7.20 (s, 2H), 2.2 (s,6H) 115

B 581 195- 199 (CDCl₃) 10.2 (s, 1H), 8.7 (s, 1H), 8.6 (s, 1H), 8.25 (d,J = 8.4 Hz, 2H), 8.0 (s, 1H), 7.82 (m, 4H), 7.4 (d, J = 8.4 Hz, 2H), 7.0(s, 2H), 3.82 (s, 3H) 116

C 541 (M + H) 202- 210 (CDCl₃) 9.88 (s, 1H), 8.61 (s, 1H), 8.60 (s, 1H),8.27 (d, J = 8.4 Hz, 2H), 7.9 (s, 1H), 7.9-7.7 (m, 4H), 7.4 (d, J = 8.6Hz, 2H), 6.7 (s, 2H), 3.81 (s, 3H), 2.33 (s, 6H) 117

C 527 (M + H) 210- 214 (CDCl₃) 9.89 (s, 1H), 9.02 (s, 1H), 8.6 (m, 3H),8.3 (d, J = 8.5 Hz, 2H), 7.9-7.8 (m, 4H), 7.43 (d, J = 8.5 Hz, 2H), 6.85(d, J = 6 Hz, 1H), 6.8 (s, 1H), 3.95 (s, 3H), 2.38 (s, 3H) 118

B 509 (M + H) 246- 249 10.65 (s, 1H), 10.07 (s, 1H), 9.40 (s, 1H), 8.5(s, 1H), 8.15-7.9 (m, 6H), 7.61 (d, J = 8.5 Hz, 2H), 6.89 (s, 2H), 2.27(s, 3H), 2.19 (s, 6H) 119

C calcd for C₂₅H₂₁F₃N₆O₃, 510.1627; found, 510.165 240- 241 10.72 (s,1H), 9.41 (s, 1H), 8.49 (s, 1H), 8.14 (d, J = 8.4 Hz, 2H), 8.09 (d, J =9.1 Hz, 2H), 8.00 (s, 1H), 7.94 (d, J = 8.4 Hz, 2H), 7.62 (d, J = 8.4Hz, 2H), 7.37 (d, J = 8.7 Hz, 1H), 6.83 (d, J = 2.8 Hz, 1H), 6.76 (dd, J= 8.7, 2.9 Hz, 1H), 3.74 (s, 3H), 2.25 (s, 3H) 120

C 535 (M + H) 222- 223 10.92 (s, 1H), 9.42 (s, 1H), 9.03 (s, 1H), 8.13(d, J = 8.5 Hz, 2H), 8.09 (d, J = 9.1 Hz, 2H), 7.99 (s, 2H), 7.97 (s,1H), 7.63 (d, J = 8.3 Hz, 2H), 7.56 (d, J = 8.1 Hz, 2H), 7.41-7.32 (m,1H) 121

B 555 (M + H) 186- 192 (CDCl₃) 10.42 (s, 1H), 8.88 (s, 1H), 8.60 (s,1H), 8.22 (d, J = 8.4 Hz, 2H), 8.0 (s, 1H), 7.9-7.7 (m, 4H), 7.45- 7.38(m, 3H), 6.9-6.7 (m, 2H), 3.83 (s, 3H), 3.12 (m, 1H), 1.25 (d, J = 6.5Hz, 6H) 122

C 577 (M + H) 197- 200 (CDCl₃) 10.2 (s, 1H), 8.90 (s, 1H), 8.62 (s, 1H),8.25 (d, J = 8.4 Hz, 2H), 7.98 (s, 1H), 7.9-7.7 (m, 4H), 7.4 (m, 3H),6.8 (m, 2H), 3.82 (s, 3H), 2.37 (s, 3H) 123

B 575 (M + H) 237- 240 (CDCl₃) 9.85 (s, 1H), 8.63 (s, 1H), 8.60 (s, 1H),8.26 (d, J = 8.4 Hz, 2H), 7.89 (s, 1H), 7.85-7.76 (m, 4H), 7.41 (d, J =8.4 Hz, 2H), 6.97 (s, 2H), 2.32 (s, 3H), 2.30 (s, 6H) 124

C 513 (M + H) 240- 248 (CDCl₃) 9.57 (s, 1H), 8.60 (s, 1H), 8.54 (s, 1H),8.26 (d, J = 8.4 Hz, 2H), 7.91 (s, 1H), 7.77 (d, J = 8.4 Hz, 2H), 7.64(d, J = 8.5 Hz, 2H), 7.33 (d, J = 8.6 Hz, 2H), 6.69 (s, 2H), 3.81 (s,3H), 2.76-2.59 (m, 2H), 2.31 (s, 6H), 1.75- 1.57 (m, 2H), 1.48-1.30 (m,2H), 0.95 (t, J = 7.3 Hz, 3H) 125

C 555 (M + H) 206- 209 (CDCl₃) 8.90 (s, 1H), 8.80 (s, 1H), 8.6 (s, 1H),8.28 (d, J = 8.4 Hz, 2H), 8.9-8.7 (m, 4H), 7.4 (d, J = 8.6 Hz, 2H), 6.7(s, 2H), 3.80 (s, 3H), 2.39 (s, 3H), 2.32 (s, 6H) 126

C 525 (M + H) 209- 215 (CDCl₃) 8.92 (s, 1H), 8.90 (s, 1H), 8.80 (s, 1H),8.26 (d, J = 8.4 Hz, 2H), 8.9-8.8 (m, 4H), 7.4 (d, J = 8.6 Hz, 2H),7.25-7.15 (m, 3H), 2.40 (s, 3H), 2.36 (s, 6H) 127

C 525 (M + H) 230- 240 (CDCl₃) 9.93 (s, 1H), 8.69 (s, 1H), 8.60 (s, 1H),8.26 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 9.5 Hz, 2H), 7.95 (s, 1H), 7.86-7.75 (m, 4H), 6.69 (s, 2H), 3.81 (s, 3H), 2.31 (s, 6H) 128

C 592 (M + H) 233- 236 (CDCl₃) 9.89 (s, 1H), 8.60 (s, 2H), 8.25 (d, J =8.5 Hz, 2H), 7.95 (s, 1H), 7.88-7.70 (m, 4H), 7.41 (d, J = 9.0 Hz, 2H),6.70 (s, 2H), 3.81 (s, 3H), 2.31 (s, 6H) 129

C 542 (M + 1) 215- 219 (CDCl₃) 9.98 (s, 1H), 8.63- 8.52 (m, 2H), 8.26(d, J = 8.5 Hz, 2H), 7.97 (s, 1H), 7.84-7.69 (m, 4H), 7.46-7.32 (m, 2H),6.53 (s, 1H), 3.93 (s, 3H), 2.45 (s, 3H), 2.29 (s, 3H) 130

C 570 (M + H) 221- 223 11.82 (s, 1H), 9.98 (s, 1H), 8.17 (s, 1H), 7.97(d, J = 8.26 Hz, 2H), 7.76 (d, J = 8.26 Hz, 2H), 7.29 (d, J = 8.22 Hz,2H), 7.18-7.04 (m, 5H), 5.22- 5.16 (m, 1H), 3.88-3.76 (m, 1H), 3.71 (s,3H), 3.64- 3.58 (m, 1H), 2.21 (s, 6H) 131

C 611 (M + H) 215- 217 12.03 (s, 1H), 10.21 (s, 1H), 8.17 (s, 1H), 7.98(d, J = 8.24 Hz, 2H), 7.76 (d, J = 8.24 Hz, 2H), 7.59-7.56 (m, 2H),7.41- 7.39 (m, 1H), 7.27 (d, J = 8.26 Hz, 2H), 7.08 (d, J = 8.26 Hz,2H), 5.22-5.19 (m, 1H), 3.84- 3.76 (m, 1H), 3.71 (s, 3H), 3.64-3.59 (m,1H) 132

C 601 (M + H) 205- 211 (CDCl₃) 9.31 (s, 1H), 8.69 (s, 1H), 8.56 (s, 1H),8.03- 7.40 (m, 6H), 7.18 (d, J = 8.4 Hz, 2H), 6.69 (s, 2H), 4.87 (dd, J= 12.7, 6.6 Hz, 1H), 3.72 (s, 3H), 3.9-3.6 (m, 2H), 3.49 (s, 3H), 2.23(s, 6H) 133

C 585 (M + H) 250 dec (CDCl₃) 9.27 (s, 1H), 8.69 (s, 1H), 8.56 (s, 1H),8.05- 7.55 (m, 6H), 7.24- 6.96 (m, 2H), 6.69 (s, 2H), 6.22 (s, 1H), 5.40(s, 1H), 4.62 (m, 1H), 3.9-3.75 (m, 1H), 3.81 (s, 3H), 3.52- 3.42 (m,1H), 2.30 (s, 6H) 134

C 509 (M + H) 200- 202 11.78 (s, 1H), 9.81 (s, 1H), 8.17 (s, 1H), 8.06(s, 1H), 7.84 (d, J = 8.24 Hz, 2H), 7.81 (d, J = 8.26 Hz, 2H), 7.76 (d,J = 8.24 Hz, 2H), 7.53-7.48 (m, 3H), 7.13- 7.09 (m, 2H), 7.04-7.02 (m,1H), 6.83- 6.80 (m, 1H), 2.21 (s, 6H) 135

C 550 (M + H) 218- 220 12.00 (s, 1H), 10.12 (s, 1H), 8.18 (s, 1H), 8.06(s, 1H), 7.89 (d, J = 8.22 Hz, 2H), 7.81 (d, J = 8.24 Hz, 2H), 7.75 (d,J = 8.24 Hz, 2H), 7.59-7.47 (m, 5H), 7.41- 7.38 (m, 1H), 6.83-6.81 (m,1H) 136

C 510 (M + H) 216- 218 11.81 (s, 1H), 9.97 (s, 1H), 8.62 (s, 1H),8.21-8.19 (m, 1H), 8.10- 8.07 (d, J = 8.26 Hz, 2H), 8.04-7.99 (m, 4H),7.58 (d, J = 8.24 Hz, 2H), 7.19- 7.06 (m, 4H), 2.21 (s, 6H) 137

C 551 (M + H) 220- 222 12.02 (s, 1H), 10.18 (s, 1H), 8.62 (s, 1H),8.19-8.17 (m, 1H), 8.09- 7.97 (m, 6H), 7.61-7.57 (m, 4H), 7.42- 7.37 (m,1H), 7.21-7.19 (m, 1H) 138

C 510 (M + H) 250- 260 (CDCl₃) 9.75 (s, 1H), 8.70 (s, 1H), 8.21 (s, 1H),8.07 (s, 1H), 7.92 (s, 1H), 7.8 (d, J = 8.4 Hz, 2H), 7.71 (d, J = 8.6Hz, 2H), 7.62 (d, J = 8.4 Hz, 2H), 7.35 (d, J = 8.6 Hz, 2H), 7.3-7.1 (m,3H), 2.33 (s, 6H) 139

C 524 (M + H) 235- 242 (CDCl₃) Major isomer: 8.87 (s, 1H), 8.85 (s, 1H),8.19 (s, 1H), 8.02 (s, 1H), 7.86- 7.74 (m, 4H), 7.6 (d, J = 8.6 Hz, 2H),7.35 (d, J = 8.3 Hz, 2H), 7.23-7.06 (m, 3H), 2.38 (s, 3H), 2.34 (s, 6H)140

C 512 (M + H) 238- 240 11.79 (s, 1H), 10.96 (s, 1H), 8.17 (s, 1H), 7.98(d, J = 8.22 Hz, 2H), 7.76 (d, J = 8.22 Hz, 2H), 7.26 (d, J = 8.26 Hz,2H), 7.18-7.06 (m, 5H), 3.97-3.91 (m, 2H), 3.39- 3.34 (m, 2H), 2.20 (s,6H) 141

C 553 (M + H) 224- 226 12.03 (s, 1H), 10.17 (s, 1H), 8.18 (s, 1H), 7.96(d, J = 8.24 Hz, 2H), 7.76 (d, J = 8.24 Hz, 2H), 7.59-7.54 (m, 2H),7.42- 7.39 (m, 1H), 7.37 (d, J = 8.26 Hz, 2H), 7.17 (d, J = 8.26 Hz,2H), 3.98-3.84 (m, 2H), 3.43- 3.37 (m, 2H) 142

B 541 (M + H) 195- 200 (CDCl₃) 10.33 (s, 1H), 8.6 (s, 1H), 8.21 (d, J =8.4 Hz, 2H), 7.92 (s, 1H), 7.8 (d, J = 8.6 Hz, 2H), 7.75 (d, J = 8.4 Hz,2H), 7.68 (d, J = 7 Hz, 1H), 7.45-7.35 (m, 4H), 6.91 (d, J = 8 Hz, 2H),5.73 (m, 1H), 3.80 (s, 3H), 1.65 (d, J = 7.2 Hz, 3H) 143

B 541 (M + H) 180- 186 (CDCl₃) 9.9 (s, 1H), 8.6 (s, 1H), 8.23 (d, J =8.4 Hz, 2H), 7.9 (s, 1H), 7.8 (d, J = 8.6 Hz, 2H), 7.75 (d, J = 8.4 Hz,2H), 7.7 (d, J = 7 Hz, 1H), 7.45- 7.35 (m, 4H), 6.91 (d, J = 8 Hz, 2H),5.73 (m, 1H), 3.80 (s, 3H), 1.65 (d, J = 12 Hz, 3H) 144

B 525 (M + H) 193- 198 (CDCl₃) 9.02 (s, 1H), 8.60 (s, 1H), 8.42 (d, J =8.4 Hz, 2H), 7.8-7.6 (m, 6H), 7.4 (d, J = 8 Hz, 2H), 7.32 (d, J = 8.5Hz, 2H), 7.21 (d, J = 8.4 Hz, 2H), 5.71 (m, 1H), 2.37 (s, 3H), 1.69 (d,J = 7.2 Hz, 3H) 145

B 523 (M + H) 160- 220 dec (CDCl₃) 10.21 (s, 1H), 8.60 (s, 1H), 8.2 (d,J = 8.4 Hz, 2H), 7.99 (s, 1H), 7.8 (d, J = 8.6 Hz, 2H), 7.8-7.6 (m, 3H),7.55- 7.2 (m, 6H), 6.17 (m, 1H), 3.2-2.8 (m, 3H), 2.1-1.95 (m, 1H) 146

B 591 (M + H) 205- 210 (CDCl₃) 9.12 (s, 1H), 8.60 (s, 1H), 8.25 (d, J =8.4 Hz, 2H), 7.78 (d, J = 8.5 Hz, 2H), 7.77 (s, 1H), 7.71 (d, J = 8.4Hz, 2H), 7.63 (d, J = 7 Hz, 1H), 7.5 (d, J = 8.5 Hz, 2H), 7.4 (d, J =8.4 Hz, 2H), 7.35 (d, J = 8.4 Hz, 2H), 5.8-5.6 (m, 1H), 1.67 (d, J = 7Hz, 3H) 147

B 525 (M + H) 209- 213 (CDCl₃) 9.27 (s, 1H), 8.6 (s, 1H), 8.25 (d, J =8.4 Hz, 2H), 7.8 (m, 3H), 7.77 (d, J = 8.6 Hz, 2H), 7.63 (d, J = 7 Hz,1H), 7.42 (d, J = 8.5 Hz, 2H), 7.4 (s, 1H), 7.35-7.22 (m, 3H), 5.78 (m,1H), 2.28 (s, 3H), 1.62 (d, J = 7 Hz, 3H) 148

B 541 (M + H) 216- 220 (CDCl₃) 9.4 (s, 1H), 8.8 (d, J = 8 Hz, 1H), 8.62(s, 1H), 8.3 (d, J = 8.4 Hz, 2H), 7.9-7.7 (m, 5H), 7.4 (d, J = 8.5 Hz,2H), 7.4-7.3 (m, 2H), 6.93 (m, 2H), 5.78 (m, 1H), 4.03 (s, 3H), 1.62 (d,J = 6 Hz, 3H) 149

B 553 (M − H) 165 dec (CDCl₃) 9.1 (s, 1H), 8.6 (s, 1H), 8.22 (d, J = 8.4Hz, 2H), 7.85-7.6 (m, 6H), 7.4 (d, J = 8.5 Hz, 2H), 7.23 (m, 2H), 6.82(d, J = 6 Hz, 1H), 5.68 (m, 1H), 3.81 (s, 3H), 2.25 (s, 3H), 1.62 (d, J= 6 Hz, 3H) 150

B 541 (M + H) 196- 203 (CDCl₃) 9.32 (s, 1H), 8.6 (s, 1H), 8.22 (d, J =8.4 Hz, 2H), 7.85-7.7 (m, 5H), 7.6 (d, J = 6 Hz, 1H), 7.4 (d, J = 8.5Hz, 2H), 7.25-7.15 (m, 2H), 6.93 (m, 1H), 5.7 (m, 1H), 3.89 (s, 3H),1.67 (d, J = 6Hz, 3H) 151

B 571 (M + H) 165 dec (CDCl₃) 9.41 (s, 1H), 8.6 (s, 1H), 8.22 (d, J =8.4 Hz, 2H), 7.85-7.6 (m, 6H), 7.4 (d, J = 8.5 Hz, 2H), 7.05 (m, 2H),6.91 (m, 1H), 5.7 (m, 1H), 3.92 (s, 3H), 3.89 (s, 3H), 1.68 (d, J = 6Hz, 3H) 152

B 511 (M + H) 201- 206 (CDCl₃) 9.32 (s, 1H), 8.61 (s, 1H), 8.27 (d, J =8.4 Hz, 2H), 7.9-7.7 (m, 6H), 7.5- 7.3 (m, 7H), 5.76 (m, 1H), 1.67 (d, J= 7 Hz, 3H) 153

B 541 (M + H) 185- 190 (CDCl₃) 9.85 (s, 1H), 8.6 (s, 1H), 8.23 (d, J =8.4 Hz, 2H), 7.9 (s, 1H), 7.87- 7.7 (m, 5H), 7.4 (d, J = 8.5 Hz, 2H),7.4-7.4 (m, 1H), 7.1-6.95 (m, 2H), 6.85 (m , 1H), 5.73 (m, 1H), 3.81 (s,3H), 1.69 (d, J = 6 Hz, 3H) 154

B 503 (M + H) 214- 218 (CDCl₃) 9.36 (s, 1H), 8.60 (s, 1H), 8.21 (d, J =8.4 Hz, 2H), 7.9- 7.7 (m, 5H), 7.4-7.25 (m, 5H), 7.2 (d, J = 3 Hz, 1H),5.0 (s, 2 H) 155

B 517 (M + H) 171- 180 9.36 (s, 1H), 8.59 (s, 1H), 8.23 (d, J = 8.4 Hz,2H), 7.85-7.77 (m, 3H), 7.72 (d, J = 8.4 Hz, 2H), 7.61 (d, J = 8.9 Hz,1H), 7.40 (d, J = 8.3 Hz, 2H), 7.35 (m, 1H), 7.30- 7.26 (m, 1H), 7.19(dd, J = 5.0, 1.3 Hz, 1H), 5.96- 5.75 (m, 1H), 1.72 (d, J = 6.8 Hz, 3H)156

B 205- 213 11.68 (s, 1H), 9.42 (s, 1H), 9.05 (br s, 1H), 8.2-8.0 (m,5H), 7.95 (d, J = 8.5 Hz, 2H), 7.6 (d, J = 8.4 Hz, 2H), 7.23 (d, J = 5Hz, 1H), 6.8 (d, J = 5 Hz, 1H), 4.9 (d, J = 6 Hz, 2H), 2.25 (s, 3H) 157

B 555 (M + H) 174- 178 (CDCl₃) 9.20 (s, 1H), 8.8 (s, 1H), 8.23 (d, J =8.4 Hz, 2H), 7.85-7.65 (m, 6H), 7.5-7.4 (m, 6H), 5.75 (q, J = 7 Hz, 1H),4.46 (s, 2H), 3.20 (s, 3H), 1.71 (d, J = 7 Hz, 3H) 158

B 512 (M + H) — 11.7 (s, 1H), 9.42 (s, 1H), 8.87 (d, J = 8.4 Hz, 1H),8.6 (s, 1H), 8.42 (d, J = 2 Hz, 1H), 8.2-7.95 (m, 7H), 7.8 (d, J = 5.4Hz, 1H), 7.6 (d, J = 8.4 Hz, 2H), 7.38 (m, 1H), 5.8 (m, 1H), 1.6 (d, J =6 Hz, 3H) 159

B 555 (M + H) 188- 191 (CDCl₃) 9.16 (s, 1H), 8.0 (s, 1H), 8.23 (d, J =8.4 Hz, 2H), 7.8 (m, 3H), 7.72 (d, J = 8.5 Hz, 2H), 7.6 (d, J = 7 Hz,1H), 7.4 (d, J = 8.6 Hz, 2H), 6.9 (m, 2H), 6.8 (d, J = 7 Hz, 1H), 5.96(s, 2H), 5.65 (m, 1H), 1.62 (d, J = 7.5 Hz, 3H) ¹All NMR data measuredin DMSO-d₆ at 300 or 400 MHz unless otherwise noted

TABLE 2 Mortality Mortality CEW BAW Mortality 50 50 GPA 200 Compoundμg/cm2 μg/cm2 ppm 1 A A B 2 A A B 3 B A B 4 A A B 5 A A B 6 A A B 7 A BB 8 A A B 9 A A B 10 A A B 11 A A B 12 A A B 13 A A B 14 A A B 15 A A B16 A A B 17 A A B 18 A A B 19 B B B 20 A A B 21 A A B 22 A A B 23 A A B24 B A B 25 A A B 26 A A B 27 A A B 28 A A B 29 A A B 30 A A B 31 B B B32 B B B 33 A A B 34 A A B 35 B B B 36 A A B 37 A A B 38 A A B 39 A A B40 A A B 41 A A B 42 A A B 43 A A B 44 B B B 45 A A B 46 A A B 47 A A B48 A A C 49 A A B 50 A A B 51 A A B 52 A A B 53 A A B 54 B B B 55 B B B56 A A B 57 A A B 58 A A B 59 B B B 60 A A C 61 A A B 62 A A B 63 A A B64 A A B 65 A A B 66 A A B 67 A A B 68 A A B 69 A A B 70 A A B 71 A A B72 A A B 73 A A B 74 A A B 75 A A B 76 A A B 77 A A B 78 A A B 79 A A B80 A A C 81 A A B 82 A A C 83 B B C 84 B B C 85 A A C 86 A A C 87 B B C88 A A C 89 A A C 90 A A C 91 A A C 92 A A C 93 A A C 94 A A C 95 A A C96 A A C 97 A A B 98 A A C 99 A A C 100 A A C 101 A A C 102 A A C 103 AA C 104 A A C 105 A A C 106 A A C 107 A A C 108 A A C 109 A A B 110 A AC 111 A A C 112 A A C 113 B B C 114 A A C 115 A A C 116 A A C 117 A A C118 A A C 119 A A B 120 A A B 121 A A C 122 A A C 123 A A C 124 A A C125 A A B 126 A A B 127 A A B 128 A A B 129 A A B 130 A A C 131 A A C132 A A B 133 A A B 134 A A C 135 A A C 136 A A C 137 A A C 138 A A C139 A A C 140 A A C 141 A A C 142 A A C 143 A A C 144 A A C 145 A A C146 A A C 147 A A C 148 A A C 149 A A C 150 A A C 151 A A C 152 A A C153 A A C 154 A A C 155 A A C 156 A A C 157 A A C 158 A A C 159 A A C

1. A molecule of the following formula:

wherein: (a) Ar₁ is (1) furanyl, phenyl, pyridazinyl, pyridyl,pyrimidinyl, thienyl, or (2) substituted furanyl, substituted phenyl,substituted pyridazinyl, substituted pyridyl, substituted pyrimidinyl,or substituted thienyl, wherein said substituted furanyl, substitutedphenyl, substituted pyridazinyl, substituted pyridyl, substitutedpyrimidinyl, and substituted thienyl, have one or more substituentsindependently selected from H, F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₁-C₆haloalkyl, C₃-C₆ cycloalkyl, C₃-C₆ halocycloalkyl, C₃-C₆ cycloalkoxy,C₃-C₆ halocycloalkoxy, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₂-C₆ alkenyl,C₂-C₆ alkynyl, S(═O)_(n)(C₁-C₆ alkyl), S(═O)_(n)(C₁-C₆ haloalkyl),OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆ haloalkyl), C(═O)NR_(x)R_(y), (C₁-C₆alkyl)NR_(x)R_(y), C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆haloalkyl), C(═O)O(C₁-C₆ haloalkyl), C(═O)(C₃-C₆ cycloalkyl),C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl), C(═O)O(C₂-C₆ alkenyl),(C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆ alkyl), C(═O)(C₁-C₆alkyl)C(═O)O(C₁-C₆ alkyl), phenyl, phenoxy, substituted phenyl, andsubstituted phenoxy, wherein such substituted phenyl and substitutedphenoxy have one or more substituents independently selected from H, F,Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl,C₃-C₆ halocycloalkyl, C₃-C₆ cycloalkoxy, C₃-C₆ halocycloalkoxy, C₁-C₆alkoxy, C₁-C₆ haloalkoxy, C₂-C₆ alkenyl, C₂-C₆ alkynyl, S(═O)_(n)(C₁-C₆alkyl), S(═O)_(n)(C₁-C₆ haloalkyl), OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆haloalkyl), C(═O)NR_(x)R_(y), (C₁-C₆ alkyl)NR_(x)R_(y), C(═O)(C₁-C₆alkyl), C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆ haloalkyl), C(═O)O(C₁-C₆haloalkyl), C(═O)(C₃-C₆ cycloalkyl), C(═O)O(C₃-C₆ cycloalkyl),C(═O)(C₂-C₆ alkenyl), C(═O)O(C₂-C₆ alkenyl), (C₁-C₆ alkyl)O(C₁-C₆alkyl), (C₁-C₆ alkyl)S(C₁-C₆ alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆alkyl) phenyl, and phenoxy; (b) Het is a 5 or 6 membered, saturated orunsaturated, heterocyclic ring, containing one or more heteroatomsindependently selected from nitrogen, sulfur, or oxygen, and where Ar₁and Ar₂ are not ortho to each other (but may be meta or para, such as,for a five membered ring they are 1,3 and for a 6 membered ring they areeither 1,3 or 1,4), and where said heterocyclic ring may also besubstituted with one or more substituents independently selected from H,OH, F, Cl, Br, I, CN, NO₂, oxo, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆cycloalkyl, C₃-C₆ halocycloalkyl, C₃-C₆ cycloalkoxy, C₃-C₆halocycloalkoxy, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₂-C₆ alkenyl, C₂-C₆alkynyl, S(═O)_(n)(C₁-C₆ alkyl), S(═O)_(n)(C₁-C₆ haloalkyl), OSO₂(C₁-C₆alkyl), OSO₂(C₁-C₆ haloalkyl), C(═O)NR_(x)R_(y), (C₁-C₆alkyl)NR_(x)R_(y), C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆haloalkyl), C(═O)O(C₁-C₆ haloalkyl), C(═O)(C₃-C₆ cycloalkyl),C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl), C(═O)O(C₂-C₆ alkenyl),(C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆ alkyl), C(═O)(C₁-C₆alkyl)C(═O)O(C₁-C₆ alkyl), phenyl, phenoxy, substituted phenyl andsubstituted phenoxy wherein such substituted phenyl and substitutedphenoxy have one or more substituents independently selected from H, F,Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl,C₃-C₆ halocycloalkyl, C₃-C₆ cycloalkoxy, C₃-C₆ halocycloalkoxy, C₁-C₆alkoxy, C₁-C₆ haloalkoxy, C₂-C₆ alkenyl, C₂-C₆ alkynyl, S(═O)_(n)(C₁-C₆alkyl), S(═O)_(n)(C₁-C₆ haloalkyl), OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆haloalkyl), C(═O)H, C(═O)NR_(x)R_(y), (C₁-C₆ alkyl)NR_(x)R_(y),C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆ haloalkyl),C(═O)O(C₁-C₆ haloalkyl), C(═O)(C₃-C₆ cycloalkyl), C(═O)O(C₃-C₆cycloalkyl), C(═O)(C₂-C₆ alkenyl), C(═O)O(C₂-C₆ alkenyl), (C₁-C₆alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆ alkyl), C(═O)(C₁-C₆alkyl)C(═O)O(C₁-C₆ alkyl), phenyl, and phenoxy; (c) Ar₂ is (1) furanyl,phenyl, pyridazinyl, pyridyl, pyrimidinyl, thienyl, or (2) substitutedfuranyl, substituted phenyl, substituted pyridazinyl, substitutedpyridyl, substituted pyrimidinyl, or substituted thienyl, wherein saidsubstituted furanyl, substituted phenyl, substituted pyridazinyl,substituted pyridyl, substituted pyrimidinyl, and substituted thienyl,have one or more substituents independently selected from H, F, Cl, Br,I, CN, NO₂, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl, C₃-C₆halocycloalkyl, C₃-C₆ cycloalkoxy, C₃-C₆ halocycloalkoxy, C₁-C₆ alkoxy,C₁-C₆ haloalkoxy, C₂-C₆ alkenyl, C₂-C₆ alkynyl, S(═O)_(n)(C₁-C₆ alkyl),S(═O)_(n)(C₁-C₆ haloalkyl), OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆ haloalkyl),C(═O)NR_(x)R_(y), (C₁-C₆ alkyl)NR_(x)R_(y), C(═O)(C₁-C₆ alkyl),C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆ haloalkyl), C(═O)O(C₁-C₆ haloalkyl),C(═O)(C₃-C₆ cycloalkyl), C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl),C(═O)O(C₂-C₆ alkenyl), (C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆ alkyl), phenyl, phenoxy,substituted phenyl and substituted phenoxy wherein such substitutedphenyl and substituted phenoxy have one or more substituentsindependently selected from H, F, Cl, Br, I, CN, NO₂, C₁-C₆ alkyl, C₁-C₆haloalkyl, C₃-C₆ cycloalkyl, C₃-C₆ halocycloalkyl, C₃-C₆hydroxycycloalkyl, C₃-C₆ cycloalkoxy, C₃-C₆ halocycloalkoxy, C₁-C₆alkoxy, C₁-C₆ haloalkoxy, C₂-C₆ alkenyl, C₂-C₆ alkynyl, S(═O)_(n)(C₁-C₆alkyl), S(═O)_(n)(C₁-C₆ haloalkyl), OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆haloalkyl), C(═O)H, C(═O)NR_(x)R_(y), (C₁-C₆ alkyl)NR_(x)R_(y),C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆ haloalkyl),C(═O)O(C₁-C₆ haloalkyl), C(═O)(C₃-C₆ cycloalkyl), C(═O)O(C₃-C₆cycloalkyl), C(═O)(C₁-C₆ haloalkyl), C(═O)(C₂-C₆ alkenyl), C(═O)O(C₂-C₆alkenyl), (C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆ alkyl),C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆ alkyl), phenyl, and phenoxy); (d) X is Oor S; (e) R1 is selected from H, CN, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆cycloalkyl, C₃-C₆ halocycloalkyl, C₃-C₆ cycloalkoxy, C₃-C₆halocycloalkoxy, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₂-C₆ alkenyl, C₂-C₆alkynyl, S(═O)_(n)(C₁-C₆ alkyl), S(═O)_(n)(C₁-C₆ haloalkyl), OSO₂(C₁-C₆alkyl), OSO₂(C₁-C₆ haloalkyl), C(═O)NR_(x)R_(y), (C₁-C₆alkyl)NR_(x)R_(y), C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆haloalkyl), C(═O)O(C₁-C₆ haloalkyl), C(═O)(C₃-C₆ cycloalkyl),C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl), C(═O)O(C₂-C₆ alkenyl),(C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆ alkyl), C(═O)(C₁-C₆alkyl)C(═O)O(C₁-C₆ alkyl), phenyl, phenoxy; (f) R2, R3 and R4 areindependently selected from H, C₁-C₆ alkyl, C₃-C₆ cycloalkyl, C₂-C₆alkenyl, C₂-C₆ alkynyl, C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl),C(═O)(C₃-C₆ cycloalkyl), C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl),C(═O)O(C₂-C₆ alkenyl), (C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆alkyl), C(═O)(C₁-C₆ alkyl)C(═O)O(C₁-C₆ alkyl), C(═O)phenyl, phenyl,C₁-C₆ alkylphenyl, C₁-C₆ alkylphenoxy, indanyl, C(═O)Het-1, Het-1,(C₁-C₆ alkyl)Het-1, or C₁-C₆ alkyl-O-Het-1, wherein each alkyl,cycloalkyl, cycloalkoxy, halocycloalkoxy, alkoxy, haloalkoxy, alkenyl,alkynyl, C₁-C₆ alkylphenyl, phenyl, phenoxy, and Het-1, are optionallysubstituted with one or more substituents independently selected from F,Cl, Br, I, CN, NO₂, NR_(x)R_(y), C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆cycloalkyl, C₃-C₆ halocycloalkyl, C₃-C₆ cycloalkoxy, C₃-C₆halocycloalkoxy, C₁-C₆ alkoxy, C₁-C₆ haloalkoxy, C₂-C₆ alkenyl, C₃-C₆cycloalkenyl, C₂-C₆ alkynyl, C₃-C₆ cycloalkynyl, S(═O)_(n)(C₁-C₆ alkyl),S(═O)_(n)(C₁-C₆ haloalkyl), S(═O)₂N(C₁-C₆ alkyl)₂, OSO₂(C₁-C₆ alkyl),OSO₂(C₁-C₆ haloalkyl), C(═O)H, C(═O)NR_(x)R_(y), (C₁-C₆alkyl)NR_(x)R_(y), C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆haloalkyl), C(═O)O(C₁-C₆ haloalkyl), C(═O)(C₃-C₆ cycloalkyl),C(═O)O(C₃-C₆ cycloalkyl), C(═O)(C₂-C₆ alkenyl), C(═O)O(C₂-C₆ alkenyl),(C₁-C₆ alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆ alkyl), C(═O)(C₁-C₆alkyl)C(═O)O(C₁-C₆ alkyl), phenyl, phenoxy, O-Het-1, and Het-1, whereinHet-1 is a 5- or 6-membered, saturated or unsaturated, heterocyclicring, containing one or more heteroatoms independently selected fromnitrogen, sulfur or oxygen, wherein R3 and R4 together can optionallyform a 3- to 8-membered saturated or unsaturated cyclic group which maycontain one or more heteroatoms selected from nitrogen, sulfur, andoxygen; (g) n=0, 1, or 2; (h) R_(x) and R_(y) are independently selectedfrom H, C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₃-C₆ cycloalkyl, C₃-C₆halocycloalkyl, C₂-C₆ alkenyl, C₂-C₆ alkynyl, S(═O)_(n)(C₁-C₆ alkyl),S(═O)_(n)(C₁-C₆ haloalkyl), OSO₂(C₁-C₆ alkyl), OSO₂(C₁-C₆ haloalkyl),C(═O)H, C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆ alkyl), C(═O)(C₁-C₆ haloalkyl),C(═O)O(C₁-C₆ haloalkyl), C(═O)(C₃-C₆ cycloalkyl), C(═O)O(C₃-C₆cycloalkyl), C(═O)(C₂-C₆ alkenyl), C(═O)O(C₂-C₆ alkenyl), (C₁-C₆alkyl)O(C₁-C₆ alkyl), (C₁-C₆ alkyl)S(C₁-C₆ alkyl), C(═O)(C₁-C₆alkyl)C(═O)O(C₁-C₆ alkyl), and phenyl.
 2. A molecule according to claim1 wherein Ar₁ is a substituted phenyl wherein said substituted phenyl,has one or more substituents independently selected from C₁-C₆ alkyl,C₁-C₆ haloalkyl, and C₁-C₆ haloalkoxy.
 3. A molecule according to claim1 wherein Het is a triazolyl, imidazolyl, pyrrolyl, or pyrazolyl.
 4. Amolecule according to claim 1 wherein Ar₂ is a phenyl.
 5. A moleculeaccording to claim 1 wherein R4 is a C₁-C₆ alkyl, C₃-C₆ cycloalkyl,C₂-C₆ alkenyl, C(═O)phenyl, C₁-C₆ alkylphenyl, Het-1, or (C₁-C₆alkyl)Het-1.
 6. A molecule according to claim 1 wherein R4 is a C₁-C₆alkyl, C₁-C₆ alkylphenyl, phenyl, or Het-1, wherein each is substitutedwith one or more substituents independently selected from F, Cl, Br, I,CN, NO₂, NR_(x)R_(y), C₁-C₆ alkyl, C₁-C₆ haloalkyl, C₁-C₆ alkoxy, C₁-C₆haloalkoxy, C₃-C₆ cycloalkenyl, S(═O)_(n)(C₁-C₆ alkyl), S(═O)_(n)(C₁-C₆haloalkyl), S(═O)₂N(C₁-C₆ alkyl)₂, C(═O)(C₁-C₆ alkyl), C(═O)O(C₁-C₆alkyl), C(═O)(C₁-C₆ haloalkyl), (C₁-C₆ alkyl)O(C₁-C₆ alkyl), phenyl,O-Het-1, and Het-1.
 7. A molecule according to claim 1 having one of thefollowing structures


8. A process to apply a molecule according to claim 1 said processcomprising applying a molecule according to claim 1, to an area tocontrol a pest, in an amount sufficient to control such pest.
 9. Aprocess according to claim 8 wherein said pest is BAW, CEW, or GPA. 10.A molecule that is a pesticidally acceptable acid addition salt, a saltderivative, a solvate, or an ester derivative, of a molecule accordingto claim
 1. 11. A molecule according to claim 1 wherein at least one His ²H or at least one C is ¹⁴C.
 12. A composition comprising a moleculeaccording to claim 1 and at least one other compound havinginsecticidal, herbicidal, acaricidal, nematicidal, or fungicidalactivity.
 13. A composition comprising a molecule according to claim 1and a seed.
 14. A process comprising applying a molecule according toclaim 1 to a genetically modified plant, or genetically-modified seed,which has been genetically modified to express one or more specializedtraits.
 15. A process comprising: orally administering; or topicallyapplying; a molecule according to claim 1, to a non-human animal, tocontrol endoparasites, ectoparasites, or both.